[{"_id":"8983","publication_identifier":{"issn":["2663-337X"]},"acknowledgement":"Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria.","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","date_updated":"2023-09-07T13:24:17Z","oa":1,"article_processing_charge":"No","abstract":[{"text":"Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers.","lang":"eng"}],"author":[{"id":"49D32318-F248-11E8-B48F-1D18A9856A87","first_name":"Shamsi","orcid":"0000-0001-6981-6938","full_name":"Emtenani, Shamsi","last_name":"Emtenani"}],"publication_status":"published","citation":{"ista":"Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria.","short":"S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020.","ama":"Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8983\">10.15479/AT:ISTA:8983</a>","mla":"Emtenani, Shamsi. <i>Metabolic Regulation of Drosophila Macrophage Tissue Invasion</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8983\">10.15479/AT:ISTA:8983</a>.","chicago":"Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8983\">https://doi.org/10.15479/AT:ISTA:8983</a>.","ieee":"S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020.","apa":"Emtenani, S. (2020). <i>Metabolic regulation of Drosophila macrophage tissue invasion</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8983\">https://doi.org/10.15479/AT:ISTA:8983</a>"},"related_material":{"record":[{"id":"8557","relation":"part_of_dissertation","status":"public"},{"status":"public","id":"6187","relation":"part_of_dissertation"}]},"ddc":["570"],"alternative_title":["ISTA Thesis"],"title":"Metabolic regulation of Drosophila macrophage tissue invasion","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"CampIT"}],"doi":"10.15479/AT:ISTA:8983","year":"2020","file_date_updated":"2021-12-31T23:30:04Z","page":"141","status":"public","supervisor":[{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus","full_name":"Siekhaus, Daria E"}],"day":"30","type":"dissertation","date_created":"2020-12-30T15:41:26Z","file":[{"file_name":"Thesis_Shamsi_Emtenani_pdfA.pdf","file_size":10848175,"embargo":"2021-12-30","date_created":"2020-12-30T15:34:01Z","checksum":"ec2797ab7a6f253b35df0572b36d1b43","date_updated":"2021-12-31T23:30:04Z","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_id":"8984","creator":"semtenan"},{"file_name":"Thesis_Shamsi_Emtenani_source file.pdf","file_size":10073648,"date_created":"2020-12-30T15:37:36Z","checksum":"cc30e6608a9815414024cf548dff3b3a","embargo_to":"open_access","date_updated":"2021-12-31T23:30:04Z","access_level":"closed","content_type":"application/pdf","relation":"source_file","creator":"semtenan","file_id":"8985"}],"degree_awarded":"PhD","has_accepted_license":"1","department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","language":[{"iso":"eng"}],"month":"12","date_published":"2020-12-30T00:00:00Z"},{"page":"381-395.e8","file_date_updated":"2020-09-22T09:51:28Z","publication":"Current Biology","issue":"3","status":"public","intvolume":"        30","type":"journal_article","day":"03","date_created":"2020-02-02T23:01:00Z","file":[{"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"8555","success":1,"access_level":"open_access","date_updated":"2020-09-22T09:51:28Z","file_size":5360135,"file_name":"2020_CurrentBiology_Tan.pdf","checksum":"16f7d51fe28f91c21e4896a2028df40b","date_created":"2020-09-22T09:51:28Z"}],"department":[{"_id":"JiFr"},{"_id":"EvBe"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Cell Press","article_type":"original","date_published":"2020-02-03T00:00:00Z","month":"02","quality_controlled":"1","oa_version":"Published Version","project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","grant_number":"742985"},{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"grant_number":"723-2015","name":"Long Term Fellowship","_id":"256FEF10-B435-11E9-9278-68D0E5697425"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank Shigeyuki Betsuyaku (University of Tsukuba), Alison Delong (Brown University), Xinnian Dong (Duke University), Dolf Weijers (Wageningen University), Yuelin Zhang (UBC), and Martine Pastuglia (Institut Jean-Pierre Bourgin) for sharing published materials; Jana Riederer for help with cantharidin physiological analysis; David Domjan for help with cloning pET28a-PIN2HL; Qing Lu for help with DARTS; Hana Kozubı´kova´ for technical support on SA derivative synthesis; Zuzana Vondra´ kova´ for technical support with tobacco cells; Lucia Strader (Washington University), Bert De Rybel (Ghent University), Bartel Vanholme (Ghent University), and Lukas Mach (BOKU) for helpful discussions; and bioimaging and life science facilities of IST Austria for continuous support. We gratefully acknowledge the Nottingham Arabidopsis Stock Center (NASC) for providing T-DNA insertional mutants. The DSC and SPR instruments were provided by the EQ-BOKU VIBT GmbH and the BOKU Core Facility for Biomolecular and Cellular Analysis, with help of Irene Schaffner. The research leading to these results has received funding from the European Union’s Horizon 2020 program (ERC grant agreement no. 742985 to J.F.) and the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734. S.T. was supported by a European Molecular Biology Organization (EMBO) long-term postdoctoral fellowship (ALTF 723-2015). O.N. was supported by the Ministry of Education, Youth and Sports of the Czech Republic (European Regional Development Fund-Project ‘‘Centre for Experimental Plant Biology’’ no. CZ.02.1.01/0.0/0.0/16_019/0000738). J. Pospısil was supported by European Regional Development Fund Project ‘‘Centre for Experimental Plant Biology’’\r\n(no. CZ.02.1.01/0.0/0.0/16_019/0000738). J. Petrasek was supported by EU Operational Programme Prague-Competitiveness (no. CZ.2.16/3.1.00/21519). ","publication_identifier":{"issn":["09609822"]},"pmid":1,"_id":"7427","article_processing_charge":"No","date_updated":"2024-03-25T23:30:20Z","volume":30,"oa":1,"author":[{"id":"2DE75584-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0471-8285","full_name":"Tan, Shutang","last_name":"Tan","first_name":"Shutang"},{"first_name":"Melinda F","last_name":"Abas","full_name":"Abas, Melinda F","id":"3CFB3B1C-F248-11E8-B48F-1D18A9856A87"},{"id":"362BF7FE-F248-11E8-B48F-1D18A9856A87","full_name":"Verstraeten, Inge","last_name":"Verstraeten","orcid":"0000-0001-7241-2328","first_name":"Inge"},{"first_name":"Matous","full_name":"Glanc, Matous","last_name":"Glanc","orcid":"0000-0003-0619-7783","id":"1AE1EA24-02D0-11E9-9BAA-DAF4881429F2"},{"id":"34F1AF46-F248-11E8-B48F-1D18A9856A87","first_name":"Gergely","last_name":"Molnar","full_name":"Molnar, Gergely"},{"id":"4800CC20-F248-11E8-B48F-1D18A9856A87","first_name":"Jakub","orcid":"0000-0003-2140-7195","full_name":"Hajny, Jakub","last_name":"Hajny"},{"full_name":"Lasák, Pavel","last_name":"Lasák","first_name":"Pavel"},{"last_name":"Petřík","full_name":"Petřík, Ivan","first_name":"Ivan"},{"first_name":"Eugenia","last_name":"Russinova","full_name":"Russinova, Eugenia"},{"first_name":"Jan","full_name":"Petrášek, Jan","last_name":"Petrášek"},{"first_name":"Ondřej","last_name":"Novák","full_name":"Novák, Ondřej"},{"last_name":"Pospíšil","full_name":"Pospíšil, Jiří","first_name":"Jiří"},{"first_name":"Jiří","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","last_name":"Friml","id":"4159519E-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"text":"Plants, like other multicellular organisms, survive through a delicate balance between growth and defense against pathogens. Salicylic acid (SA) is a major defense signal in plants, and the perception mechanism as well as downstream signaling activating the immune response are known. Here, we identify a parallel SA signaling that mediates growth attenuation. SA directly binds to A subunits of protein phosphatase 2A (PP2A), inhibiting activity of this complex. Among PP2A targets, the PIN2 auxin transporter is hyperphosphorylated in response to SA, leading to changed activity of this important growth regulator. Accordingly, auxin transport and auxin-mediated root development, including growth, gravitropic response, and lateral root organogenesis, are inhibited. This study reveals how SA, besides activating immunity, concomitantly attenuates growth through crosstalk with the auxin distribution network. Further analysis of this dual role of SA and characterization of additional SA-regulated PP2A targets will provide further insights into mechanisms maintaining a balance between growth and defense.","lang":"eng"}],"citation":{"short":"S. Tan, M.F. Abas, I. Verstraeten, M. Glanc, G. Molnar, J. Hajny, P. Lasák, I. Petřík, E. Russinova, J. Petrášek, O. Novák, J. Pospíšil, J. Friml, Current Biology 30 (2020) 381–395.e8.","ista":"Tan S, Abas MF, Verstraeten I, Glanc M, Molnar G, Hajny J, Lasák P, Petřík I, Russinova E, Petrášek J, Novák O, Pospíšil J, Friml J. 2020. Salicylic acid targets protein phosphatase 2A to attenuate growth in plants. Current Biology. 30(3), 381–395.e8.","ama":"Tan S, Abas MF, Verstraeten I, et al. Salicylic acid targets protein phosphatase 2A to attenuate growth in plants. <i>Current Biology</i>. 2020;30(3):381-395.e8. doi:<a href=\"https://doi.org/10.1016/j.cub.2019.11.058\">10.1016/j.cub.2019.11.058</a>","mla":"Tan, Shutang, et al. “Salicylic Acid Targets Protein Phosphatase 2A to Attenuate Growth in Plants.” <i>Current Biology</i>, vol. 30, no. 3, Cell Press, 2020, p. 381–395.e8, doi:<a href=\"https://doi.org/10.1016/j.cub.2019.11.058\">10.1016/j.cub.2019.11.058</a>.","chicago":"Tan, Shutang, Melinda F Abas, Inge Verstraeten, Matous Glanc, Gergely Molnar, Jakub Hajny, Pavel Lasák, et al. “Salicylic Acid Targets Protein Phosphatase 2A to Attenuate Growth in Plants.” <i>Current Biology</i>. Cell Press, 2020. <a href=\"https://doi.org/10.1016/j.cub.2019.11.058\">https://doi.org/10.1016/j.cub.2019.11.058</a>.","ieee":"S. Tan <i>et al.</i>, “Salicylic acid targets protein phosphatase 2A to attenuate growth in plants,” <i>Current Biology</i>, vol. 30, no. 3. Cell Press, p. 381–395.e8, 2020.","apa":"Tan, S., Abas, M. F., Verstraeten, I., Glanc, M., Molnar, G., Hajny, J., … Friml, J. (2020). Salicylic acid targets protein phosphatase 2A to attenuate growth in plants. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2019.11.058\">https://doi.org/10.1016/j.cub.2019.11.058</a>"},"publication_status":"published","ddc":["580"],"related_material":{"record":[{"relation":"dissertation_contains","id":"8822","status":"public"}]},"isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"external_id":{"pmid":["31956021"],"isi":["000511287900018"]},"title":"Salicylic acid targets protein phosphatase 2A to attenuate growth in plants","ec_funded":1,"year":"2020","doi":"10.1016/j.cub.2019.11.058","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}]},{"file_date_updated":"2020-07-14T12:47:59Z","publication":"eLife","status":"public","intvolume":"         9","type":"journal_article","day":"23","date_created":"2020-02-16T23:00:50Z","file":[{"access_level":"open_access","date_updated":"2020-07-14T12:47:59Z","checksum":"2052daa4be5019534f3a42f200a09f32","date_created":"2020-02-18T07:21:16Z","file_size":7247468,"file_name":"2020_eLife_Narasimhan.pdf","file_id":"7494","creator":"dernst","relation":"main_file","content_type":"application/pdf"}],"department":[{"_id":"JiFr"},{"_id":"GaTk"},{"_id":"EM-Fac"},{"_id":"SyCr"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"publisher":"eLife Sciences Publications","scopus_import":"1","article_type":"original","date_published":"2020-01-23T00:00:00Z","month":"01","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"742985"},{"grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF"}],"quality_controlled":"1","pmid":1,"_id":"7490","publication_identifier":{"eissn":["2050-084X"]},"date_updated":"2023-08-18T06:33:07Z","oa":1,"volume":9,"article_processing_charge":"No","author":[{"id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8600-0671","last_name":"Narasimhan","full_name":"Narasimhan, Madhumitha","first_name":"Madhumitha"},{"first_name":"Alexander J","orcid":"0000-0002-2739-8843","last_name":"Johnson","full_name":"Johnson, Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Roshan","full_name":"Prizak, Roshan","last_name":"Prizak","id":"4456104E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","last_name":"Kaufmann","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"id":"2DE75584-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0471-8285","full_name":"Tan, Shutang","last_name":"Tan","first_name":"Shutang"},{"last_name":"Casillas Perez","full_name":"Casillas Perez, Barbara E","first_name":"Barbara E","id":"351ED2AA-F248-11E8-B48F-1D18A9856A87"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří","first_name":"Jiří"}],"abstract":[{"lang":"eng","text":"In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes."}],"publication_status":"published","citation":{"chicago":"Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann, Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>.","apa":"Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas Perez, B. E., &#38; Friml, J. (2020). Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>","ieee":"M. Narasimhan <i>et al.</i>, “Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","ista":"Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE, Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 9, e52067.","short":"M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas Perez, J. Friml, ELife 9 (2020).","ama":"Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>","mla":"Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>, vol. 9, e52067, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>."},"ddc":["570","580"],"article_number":"e52067","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"external_id":{"pmid":["31971511"],"isi":["000514104100001"]},"title":"Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants","ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"doi":"10.7554/eLife.52067","year":"2020"},{"citation":{"short":"U. Bezeljak, H. Loya, B.M. Kaczmarek, T.E. Saunders, M. Loose, Proceedings of the National Academy of Sciences 117 (2020) 6504–6549.","ista":"Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. 2020. Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences. 117(12), 6504–6549.","ama":"Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. Stochastic activation and bistability in a Rab GTPase regulatory network. <i>Proceedings of the National Academy of Sciences</i>. 2020;117(12):6504-6549. doi:<a href=\"https://doi.org/10.1073/pnas.1921027117\">10.1073/pnas.1921027117</a>","mla":"Bezeljak, Urban, et al. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” <i>Proceedings of the National Academy of Sciences</i>, vol. 117, no. 12, Proceedings of the National Academy of Sciences, 2020, pp. 6504–49, doi:<a href=\"https://doi.org/10.1073/pnas.1921027117\">10.1073/pnas.1921027117</a>.","chicago":"Bezeljak, Urban, Hrushikesh Loya, Beata M Kaczmarek, Timothy E. Saunders, and Martin Loose. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences, 2020. <a href=\"https://doi.org/10.1073/pnas.1921027117\">https://doi.org/10.1073/pnas.1921027117</a>.","apa":"Bezeljak, U., Loya, H., Kaczmarek, B. M., Saunders, T. E., &#38; Loose, M. (2020). Stochastic activation and bistability in a Rab GTPase regulatory network. <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1921027117\">https://doi.org/10.1073/pnas.1921027117</a>","ieee":"U. Bezeljak, H. Loya, B. M. Kaczmarek, T. E. Saunders, and M. Loose, “Stochastic activation and bistability in a Rab GTPase regulatory network,” <i>Proceedings of the National Academy of Sciences</i>, vol. 117, no. 12. Proceedings of the National Academy of Sciences, pp. 6504–6549, 2020."},"publication_status":"published","abstract":[{"lang":"eng","text":"The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell."}],"author":[{"first_name":"Urban","last_name":"Bezeljak","full_name":"Bezeljak, Urban","orcid":"0000-0003-1365-5631","id":"2A58201A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Loya","full_name":"Loya, Hrushikesh","first_name":"Hrushikesh"},{"id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","first_name":"Beata M","last_name":"Kaczmarek","full_name":"Kaczmarek, Beata M"},{"first_name":"Timothy E.","last_name":"Saunders","full_name":"Saunders, Timothy E."},{"first_name":"Martin","orcid":"0000-0001-7309-9724","last_name":"Loose","full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","date_updated":"2023-09-07T13:17:06Z","oa":1,"volume":117,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"_id":"7580","quality_controlled":"1","oa_version":"Preprint","project":[{"_id":"2599F062-B435-11E9-9278-68D0E5697425","name":"Reconstitution of cell polarity and axis determination in a cell-free system","grant_number":"RGY0083/2016"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2020","doi":"10.1073/pnas.1921027117","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"title":"Stochastic activation and bistability in a Rab GTPase regulatory network","external_id":{"isi":["000521821800040"]},"isi":1,"main_file_link":[{"url":"https://doi.org/10.1101/776567","open_access":"1"}],"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/proteins-as-molecular-switches/"}],"record":[{"relation":"dissertation_contains","id":"8341","status":"public"}]},"day":"24","type":"journal_article","intvolume":"       117","status":"public","publication":"Proceedings of the National Academy of Sciences","issue":"12","page":"6504-6549","month":"03","article_type":"original","date_published":"2020-03-24T00:00:00Z","scopus_import":"1","publisher":"Proceedings of the National Academy of Sciences","language":[{"iso":"eng"}],"department":[{"_id":"MaLo"},{"_id":"CaBe"}],"date_created":"2020-03-12T05:32:26Z"},{"ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2020","doi":"10.1038/s41477-020-0648-9","external_id":{"isi":["000531787500006"],"pmid":["32393881"]},"title":"The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/755504"}],"isi":1,"related_material":{"link":[{"url":"https://doi.org/10.1038/s41477-020-0719-y","relation":"erratum"}]},"publication_status":"published","citation":{"mla":"Tan, Shutang, et al. “The Lipid Code-Dependent Phosphoswitch PDK1–D6PK Activates PIN-Mediated Auxin Efflux in Arabidopsis.” <i>Nature Plants</i>, vol. 6, Springer Nature, 2020, pp. 556–69, doi:<a href=\"https://doi.org/10.1038/s41477-020-0648-9\">10.1038/s41477-020-0648-9</a>.","ama":"Tan S, Zhang X, Kong W, et al. The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis. <i>Nature Plants</i>. 2020;6:556-569. doi:<a href=\"https://doi.org/10.1038/s41477-020-0648-9\">10.1038/s41477-020-0648-9</a>","ista":"Tan S, Zhang X, Kong W, Yang X-L, Molnar G, Vondráková Z, Filepová R, Petrášek J, Friml J, Xue H-W. 2020. The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis. Nature Plants. 6, 556–569.","short":"S. Tan, X. Zhang, W. Kong, X.-L. Yang, G. Molnar, Z. Vondráková, R. Filepová, J. Petrášek, J. Friml, H.-W. Xue, Nature Plants 6 (2020) 556–569.","apa":"Tan, S., Zhang, X., Kong, W., Yang, X.-L., Molnar, G., Vondráková, Z., … Xue, H.-W. (2020). The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis. <i>Nature Plants</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41477-020-0648-9\">https://doi.org/10.1038/s41477-020-0648-9</a>","ieee":"S. Tan <i>et al.</i>, “The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis,” <i>Nature Plants</i>, vol. 6. Springer Nature, pp. 556–569, 2020.","chicago":"Tan, Shutang, Xixi Zhang, Wei Kong, Xiao-Li Yang, Gergely Molnar, Zuzana Vondráková, Roberta Filepová, Jan Petrášek, Jiří Friml, and Hong-Wei Xue. “The Lipid Code-Dependent Phosphoswitch PDK1–D6PK Activates PIN-Mediated Auxin Efflux in Arabidopsis.” <i>Nature Plants</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41477-020-0648-9\">https://doi.org/10.1038/s41477-020-0648-9</a>."},"author":[{"full_name":"Tan, Shutang","last_name":"Tan","orcid":"0000-0002-0471-8285","first_name":"Shutang","id":"2DE75584-F248-11E8-B48F-1D18A9856A87"},{"id":"61A66458-47E9-11EA-85BA-8AEAAF14E49A","first_name":"Xixi","orcid":"0000-0001-7048-4627","last_name":"Zhang","full_name":"Zhang, Xixi"},{"full_name":"Kong, Wei","last_name":"Kong","first_name":"Wei"},{"full_name":"Yang, Xiao-Li","last_name":"Yang","first_name":"Xiao-Li"},{"id":"34F1AF46-F248-11E8-B48F-1D18A9856A87","last_name":"Molnar","full_name":"Molnar, Gergely","first_name":"Gergely"},{"first_name":"Zuzana","last_name":"Vondráková","full_name":"Vondráková, Zuzana"},{"last_name":"Filepová","full_name":"Filepová, Roberta","first_name":"Roberta"},{"full_name":"Petrášek, Jan","last_name":"Petrášek","first_name":"Jan"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří"},{"full_name":"Xue, Hong-Wei","last_name":"Xue","first_name":"Hong-Wei"}],"abstract":[{"text":"Directional intercellular transport of the phytohormone auxin mediated by PIN FORMED (PIN) efflux carriers plays essential roles in both coordinating patterning processes and integrating multiple external cues by rapidly redirecting auxin fluxes. Multilevel regulations of PIN activity under internal and external cues are complicated; however, the underlying molecular mechanism remains elusive. Here we demonstrate that 3’-Phosphoinositide-Dependent Protein Kinase1 (PDK1), which is conserved in plants and mammals, functions as a molecular hub integrating the upstream lipid signalling and the downstream substrate activity through phosphorylation. Genetic analysis uncovers that loss-of-function Arabidopsis mutant pdk1.1 pdk1.2 exhibits a plethora of abnormalities in organogenesis and growth, due to the defective PIN-dependent auxin transport. Further cellular and biochemical analyses reveal that PDK1 phosphorylates D6 Protein Kinase to facilitate its activity towards PIN proteins. Our studies establish a lipid-dependent phosphorylation cascade connecting membrane composition-based cellular signalling with plant growth and patterning by regulating morphogenetic auxin fluxes.","lang":"eng"}],"oa":1,"volume":6,"date_updated":"2023-08-18T07:05:57Z","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"742985"},{"grant_number":"723-2015","name":"Long Term Fellowship","_id":"256FEF10-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","oa_version":"Preprint","_id":"7600","pmid":1,"publication_identifier":{"eissn":["20550278"]},"date_published":"2020-05-01T00:00:00Z","article_type":"original","month":"05","language":[{"iso":"eng"}],"publisher":"Springer Nature","scopus_import":"1","department":[{"_id":"JiFr"}],"date_created":"2020-03-21T16:34:16Z","type":"journal_article","day":"01","status":"public","intvolume":"         6","page":"556-569","publication":"Nature Plants"},{"page":"1644-1664","publication":"The Plant Cell","issue":"5","type":"journal_article","day":"01","status":"public","intvolume":"        32","department":[{"_id":"JiFr"}],"date_created":"2020-03-28T07:39:22Z","date_published":"2020-05-01T00:00:00Z","article_type":"original","month":"05","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"American Society of Plant Biologists","article_processing_charge":"No","oa":1,"date_updated":"2023-09-05T12:21:06Z","volume":32,"quality_controlled":"1","oa_version":"Published Version","project":[{"grant_number":"742985","call_identifier":"H2020","_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"},{"call_identifier":"FWF","name":"Molecular mechanisms of endocytic cargo recognition in plants","_id":"26538374-B435-11E9-9278-68D0E5697425","grant_number":"I03630"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"eissn":["1532-298X"],"issn":["1040-4651"]},"_id":"7619","pmid":1,"citation":{"ama":"Zhang X, Adamowski M, Marhavá P, et al. Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters. <i>The Plant Cell</i>. 2020;32(5):1644-1664. doi:<a href=\"https://doi.org/10.1105/tpc.19.00869\">10.1105/tpc.19.00869</a>","mla":"Zhang, Xixi, et al. “Arabidopsis Flippases Cooperate with ARF GTPase Exchange Factors to Regulate the Trafficking and Polarity of PIN Auxin Transporters.” <i>The Plant Cell</i>, vol. 32, no. 5, American Society of Plant Biologists, 2020, pp. 1644–64, doi:<a href=\"https://doi.org/10.1105/tpc.19.00869\">10.1105/tpc.19.00869</a>.","short":"X. Zhang, M. Adamowski, P. Marhavá, S. Tan, Y. Zhang, L. Rodriguez Solovey, M. Zwiewka, V. Pukyšová, A.S. Sánchez, V.K. Raxwal, C.S. Hardtke, T. Nodzynski, J. Friml, The Plant Cell 32 (2020) 1644–1664.","ista":"Zhang X, Adamowski M, Marhavá P, Tan S, Zhang Y, Rodriguez Solovey L, Zwiewka M, Pukyšová V, Sánchez AS, Raxwal VK, Hardtke CS, Nodzynski T, Friml J. 2020. Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters. The Plant Cell. 32(5), 1644–1664.","apa":"Zhang, X., Adamowski, M., Marhavá, P., Tan, S., Zhang, Y., Rodriguez Solovey, L., … Friml, J. (2020). Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters. <i>The Plant Cell</i>. American Society of Plant Biologists. <a href=\"https://doi.org/10.1105/tpc.19.00869\">https://doi.org/10.1105/tpc.19.00869</a>","ieee":"X. Zhang <i>et al.</i>, “Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters,” <i>The Plant Cell</i>, vol. 32, no. 5. American Society of Plant Biologists, pp. 1644–1664, 2020.","chicago":"Zhang, Xixi, Maciek Adamowski, Petra Marhavá, Shutang Tan, Yuzhou Zhang, Lesia Rodriguez Solovey, Marta Zwiewka, et al. “Arabidopsis Flippases Cooperate with ARF GTPase Exchange Factors to Regulate the Trafficking and Polarity of PIN Auxin Transporters.” <i>The Plant Cell</i>. American Society of Plant Biologists, 2020. <a href=\"https://doi.org/10.1105/tpc.19.00869\">https://doi.org/10.1105/tpc.19.00869</a>."},"publication_status":"published","author":[{"full_name":"Zhang, Xixi","last_name":"Zhang","orcid":"0000-0001-7048-4627","first_name":"Xixi","id":"61A66458-47E9-11EA-85BA-8AEAAF14E49A"},{"id":"45F536D2-F248-11E8-B48F-1D18A9856A87","first_name":"Maciek","orcid":"0000-0001-6463-5257","full_name":"Adamowski, Maciek","last_name":"Adamowski"},{"id":"44E59624-F248-11E8-B48F-1D18A9856A87","last_name":"Marhavá","full_name":"Marhavá, Petra","first_name":"Petra"},{"orcid":"0000-0002-0471-8285","full_name":"Tan, Shutang","last_name":"Tan","first_name":"Shutang","id":"2DE75584-F248-11E8-B48F-1D18A9856A87"},{"id":"3B6137F2-F248-11E8-B48F-1D18A9856A87","first_name":"Yuzhou","full_name":"Zhang, Yuzhou","last_name":"Zhang","orcid":"0000-0003-2627-6956"},{"full_name":"Rodriguez Solovey, Lesia","last_name":"Rodriguez Solovey","orcid":"0000-0002-7244-7237","first_name":"Lesia","id":"3922B506-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Zwiewka","full_name":"Zwiewka, Marta","first_name":"Marta"},{"full_name":"Pukyšová, Vendula","last_name":"Pukyšová","first_name":"Vendula"},{"first_name":"Adrià Sans","full_name":"Sánchez, Adrià Sans","last_name":"Sánchez"},{"first_name":"Vivek Kumar","last_name":"Raxwal","full_name":"Raxwal, Vivek Kumar"},{"last_name":"Hardtke","full_name":"Hardtke, Christian S.","first_name":"Christian S."},{"first_name":"Tomasz","last_name":"Nodzynski","full_name":"Nodzynski, Tomasz"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří","first_name":"Jiří"}],"abstract":[{"text":"Cell polarity is a fundamental feature of all multicellular organisms. In plants, prominent cell polarity markers are PIN auxin transporters crucial for plant development. To identify novel components involved in cell polarity establishment and maintenance, we carried out a forward genetic screening with PIN2:PIN1-HA;pin2 Arabidopsis plants, which ectopically express predominantly basally localized PIN1 in the root epidermal cells leading to agravitropic root growth. From the screen, we identified the regulator of PIN polarity 12 (repp12) mutation, which restored gravitropic root growth and caused PIN1-HA polarity switch from basal to apical side of root epidermal cells. Complementation experiments established the repp12 causative mutation as an amino acid substitution in Aminophospholipid ATPase3 (ALA3), a phospholipid flippase with predicted function in vesicle formation. ala3 T-DNA mutants show defects in many auxin-regulated processes, in asymmetric auxin distribution and in PIN trafficking. Analysis of quintuple and sextuple mutants confirmed a crucial role of ALA proteins in regulating plant development and in PIN trafficking and polarity. Genetic and physical interaction studies revealed that ALA3 functions together with GNOM and BIG3 ARF GEFs. Taken together, our results identified ALA3 flippase as an important interactor and regulator of ARF GEF functioning in PIN polarity, trafficking and auxin-mediated development.","lang":"eng"}],"isi":1,"main_file_link":[{"url":"https://doi.org/10.1105/tpc.19.00869","open_access":"1"}],"ec_funded":1,"year":"2020","doi":"10.1105/tpc.19.00869","acknowledged_ssus":[{"_id":"Bio"}],"title":"Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters","external_id":{"pmid":["32193204"],"isi":["000545741500030"]}},{"type":"preprint","publication_status":"published","citation":{"chicago":"Slovakova, Jana, Mateusz K Sikora, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Karla Huljev, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.11.20.391284\">https://doi.org/10.1101/2020.11.20.391284</a>.","ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","apa":"Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W., Huljev, K., &#38; Heisenberg, C.-P. J. (2020). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.11.20.391284\">https://doi.org/10.1101/2020.11.20.391284</a>","short":"J. Slovakova, M.K. Sikora, S. Caballero Mancebo, G. Krens, W. Kaufmann, K. Huljev, C.-P.J. Heisenberg, BioRxiv (2020).","ista":"Slovakova J, Sikora MK, Caballero Mancebo S, Krens G, Kaufmann W, Huljev K, Heisenberg C-PJ. 2020. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv, <a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>.","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>.","ama":"Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>"},"day":"20","author":[{"first_name":"Jana","last_name":"Slovakova","full_name":"Slovakova, Jana","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sikora","full_name":"Sikora, Mateusz K","first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","last_name":"Caballero Mancebo","full_name":"Caballero Mancebo, Silvia","orcid":"0000-0002-5223-3346","first_name":"Silvia"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","orcid":"0000-0003-4761-5996","last_name":"Krens","full_name":"Krens, Gabriel"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","last_name":"Kaufmann"},{"last_name":"Huljev","full_name":"Huljev, Karla","first_name":"Karla","id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566"}],"status":"public","abstract":[{"lang":"eng","text":"Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact."}],"date_updated":"2024-03-25T23:30:10Z","oa":1,"page":"41","article_processing_charge":"No","publication":"bioRxiv","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","acknowledgement":"We would like to thank Edouard Hannezo for discussions, Shayan Shami Pour and Daniel Capek for help with data analysis, Vanessa Barone and other members of the Heisenberg laboratory for thoughtful discussions and comments on the manuscript. We also thank Jack Merrin for preparing the microwells, and the Scientific Service Units at IST Austria, specifically Bioimaging and Electron Microscopy, and the Zebrafish Facility for continuous support. We acknowledge Hitoshi Morita for the kind gift of VinculinB-GFP plasmid. This research was supported by an ERC Advanced Grant (MECSPEC) to C.-P.H, EMBO Long Term grant (ALTF 187-2013) to M.S and IST Fellow Marie-Curie COFUND No. P_IST_EU01 to J.S.","oa_version":"Preprint","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"grant_number":"742573","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425"},{"grant_number":"187-2013","_id":"2521E28E-B435-11E9-9278-68D0E5697425","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension"}],"_id":"9750","date_published":"2020-11-20T00:00:00Z","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"SSU"}],"year":"2020","month":"11","doi":"10.1101/2020.11.20.391284","language":[{"iso":"eng"}],"publisher":"Cold Spring Harbor Laboratory","title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"main_file_link":[{"url":"https://doi.org/10.1101/2020.11.20.391284","open_access":"1"}],"date_created":"2021-07-29T11:29:50Z","related_material":{"record":[{"status":"public","id":"10766","relation":"later_version"},{"relation":"dissertation_contains","id":"9623","status":"public"}]}},{"ec_funded":1,"year":"2019","doi":"10.3390/biom9060222","acknowledged_ssus":[{"_id":"Bio"}],"external_id":{"isi":["000475301500018"],"pmid":["31181636"]},"title":"PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton","article_number":"222","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["580"],"citation":{"ama":"Glanc M, Fendrych M, Friml J. PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton. <i>Biomolecules</i>. 2019;9(6). doi:<a href=\"https://doi.org/10.3390/biom9060222\">10.3390/biom9060222</a>","mla":"Glanc, Matous, et al. “PIN2 Polarity Establishment in Arabidopsis in the Absence of an Intact Cytoskeleton.” <i>Biomolecules</i>, vol. 9, no. 6, 222, MDPI, 2019, doi:<a href=\"https://doi.org/10.3390/biom9060222\">10.3390/biom9060222</a>.","short":"M. Glanc, M. Fendrych, J. Friml, Biomolecules 9 (2019).","ista":"Glanc M, Fendrych M, Friml J. 2019. PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton. Biomolecules. 9(6), 222.","apa":"Glanc, M., Fendrych, M., &#38; Friml, J. (2019). PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton. <i>Biomolecules</i>. MDPI. <a href=\"https://doi.org/10.3390/biom9060222\">https://doi.org/10.3390/biom9060222</a>","ieee":"M. Glanc, M. Fendrych, and J. Friml, “PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton,” <i>Biomolecules</i>, vol. 9, no. 6. MDPI, 2019.","chicago":"Glanc, Matous, Matyas Fendrych, and Jiří Friml. “PIN2 Polarity Establishment in Arabidopsis in the Absence of an Intact Cytoskeleton.” <i>Biomolecules</i>. MDPI, 2019. <a href=\"https://doi.org/10.3390/biom9060222\">https://doi.org/10.3390/biom9060222</a>."},"publication_status":"published","author":[{"id":"1AE1EA24-02D0-11E9-9BAA-DAF4881429F2","last_name":"Glanc","full_name":"Glanc, Matous","orcid":"0000-0003-0619-7783","first_name":"Matous"},{"first_name":"Matyas","orcid":"0000-0002-9767-8699","last_name":"Fendrych","full_name":"Fendrych, Matyas","id":"43905548-F248-11E8-B48F-1D18A9856A87"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","last_name":"Friml"}],"abstract":[{"text":"Cell polarity is crucial for the coordinated development of all multicellular organisms. In plants, this is exemplified by the PIN-FORMED (PIN) efflux carriers of the phytohormone auxin: The polar subcellular localization of the PINs is instructive to the directional intercellular auxin transport, and thus to a plethora of auxin-regulated growth and developmental processes. Despite its importance, the regulation of PIN polar subcellular localization remains poorly understood. Here, we have employed advanced live-cell imaging techniques to study the roles of microtubules and actin microfilaments in the establishment of apical polar localization of PIN2 in the epidermis of the Arabidopsis root meristem. We report that apical PIN2 polarity requires neither intact actin microfilaments nor microtubules, suggesting that the primary spatial cue for polar PIN distribution is likely independent of cytoskeleton-guided endomembrane trafficking.","lang":"eng"}],"article_processing_charge":"No","volume":9,"date_updated":"2023-08-28T12:30:24Z","oa":1,"project":[{"call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985"}],"oa_version":"Published Version","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"_id":"6611","date_published":"2019-06-07T00:00:00Z","month":"06","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"MDPI","department":[{"_id":"JiFr"}],"has_accepted_license":"1","file":[{"content_type":"application/pdf","relation":"main_file","creator":"kschuh","file_id":"6625","file_name":"biomolecules-2019-Matous.pdf","file_size":1066773,"date_created":"2019-07-08T15:46:32Z","checksum":"1ce1bd36038fe5381057a1bcc6760083","date_updated":"2020-07-14T12:47:34Z","access_level":"open_access"}],"date_created":"2019-07-07T21:59:21Z","type":"journal_article","day":"07","status":"public","intvolume":"         9","file_date_updated":"2020-07-14T12:47:34Z","publication":"Biomolecules","issue":"6"},{"day":"09","type":"dissertation","status":"public","supervisor":[{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari"}],"file_date_updated":"2021-02-10T23:30:09Z","page":"97","month":"09","date_published":"2019-09-09T00:00:00Z","publisher":"Institute of Science and Technology Austria","language":[{"iso":"eng"}],"has_accepted_license":"1","degree_awarded":"PhD","department":[{"_id":"JoCs"}],"file":[{"embargo_to":"open_access","date_updated":"2021-02-10T23:30:09Z","access_level":"closed","file_name":"Thesis_Damaris_Rangel_source.docx","file_size":18253100,"date_created":"2019-09-09T13:09:45Z","checksum":"244dc4f74dbfc94f414156092298831f","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","creator":"drangel","file_id":"6865"},{"creator":"drangel","file_id":"6866","content_type":"application/pdf","request_a_copy":0,"relation":"main_file","date_updated":"2020-09-11T22:30:04Z","access_level":"open_access","date_created":"2019-09-09T13:09:52Z","checksum":"59c73be40eeaa1c4db24067270151555","file_name":"Thesis_Damaris_Rangel_pdfa.pdf","file_size":2160109,"embargo":"2020-09-10"}],"date_created":"2019-09-06T06:54:16Z","citation":{"chicago":"Rangel Guerrero, Dámaris K. “The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6849\">https://doi.org/10.15479/AT:ISTA:6849</a>.","apa":"Rangel Guerrero, D. K. (2019). <i>The role of CCK-interneurons in regulating hippocampal network dynamics</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6849\">https://doi.org/10.15479/AT:ISTA:6849</a>","ieee":"D. K. Rangel Guerrero, “The role of CCK-interneurons in regulating hippocampal network dynamics,” Institute of Science and Technology Austria, 2019.","ista":"Rangel Guerrero DK. 2019. The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria.","short":"D.K. Rangel Guerrero, The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics, Institute of Science and Technology Austria, 2019.","ama":"Rangel Guerrero DK. The role of CCK-interneurons in regulating hippocampal network dynamics. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6849\">10.15479/AT:ISTA:6849</a>","mla":"Rangel Guerrero, Dámaris K. <i>The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6849\">10.15479/AT:ISTA:6849</a>."},"publication_status":"published","abstract":[{"text":"Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. ","lang":"eng"}],"author":[{"id":"4871BCE6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8602-4374","last_name":"Rangel Guerrero","full_name":"Rangel Guerrero, Dámaris K","first_name":"Dámaris K"}],"article_processing_charge":"No","oa":1,"date_updated":"2023-09-19T10:01:12Z","publication_identifier":{"issn":["2663-337X"],"isbn":["9783990780039"]},"_id":"6849","oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2019","doi":"10.15479/AT:ISTA:6849","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"M-Shop"}],"title":"The role of CCK-interneurons in regulating hippocampal network dynamics","alternative_title":["ISTA Thesis"],"related_material":{"record":[{"relation":"part_of_dissertation","id":"5914","status":"public"}]},"ddc":["570"]},{"date_created":"2019-09-22T22:00:36Z","department":[{"_id":"EvBe"}],"language":[{"iso":"eng"}],"publisher":"The Company of Biologists","scopus_import":"1","article_type":"original","date_published":"2019-09-12T00:00:00Z","month":"09","issue":"17","publication":"Development","status":"public","intvolume":"       146","type":"journal_article","day":"12","article_number":"dev175919","isi":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1242/dev.175919"}],"title":"Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis","external_id":{"isi":["000486297400011"],"pmid":["31391194"]},"ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"doi":"10.1242/dev.175919","year":"2019","acknowledgement":"We thank Jiri Friml and Phillip Brewer for inspiring discussion and for help in preparing the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Bioimaging Facility\r\n(BIF), the Life Science Facility (LSF).\r\nThis work was supported by grants from the European Research Council (Starting Independent Research Grant ERC-2007-Stg- 207362-HCPO to E.B.). J.P. and M.S. received funds from European Regional Development Fund-Project ‘Centre for Experimental Plant Biology’ (No. CZ.02.1.01/0.0/0.0/16_019/0000738).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","quality_controlled":"1","project":[{"call_identifier":"FP7","_id":"253FCA6A-B435-11E9-9278-68D0E5697425","name":"Hormonal cross-talk in plant organogenesis","grant_number":"207362"}],"_id":"6897","pmid":1,"publication_identifier":{"eissn":["14779129"]},"oa":1,"date_updated":"2025-05-07T11:10:55Z","volume":146,"article_processing_charge":"No","author":[{"first_name":"Qiang","last_name":"Zhu","full_name":"Zhu, Qiang","id":"40A4B9E6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-4675-6893","full_name":"Gallemi, Marçal","last_name":"Gallemi","first_name":"Marçal","id":"460C6802-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pospíšil, Jiří","last_name":"Pospíšil","first_name":"Jiří"},{"full_name":"Žádníková, Petra","last_name":"Žádníková","first_name":"Petra"},{"last_name":"Strnad","full_name":"Strnad, Miroslav","first_name":"Miroslav"},{"first_name":"Eva","orcid":"0000-0002-8510-9739","last_name":"Benková","full_name":"Benková, Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"lang":"eng","text":"The apical hook is a transiently formed structure that plays a protective role when the germinating seedling penetrates through the soil towards the surface. Crucial for proper bending is the local auxin maxima, which defines the concave (inner) side of the hook curvature. As no sign of asymmetric auxin distribution has been reported in embryonic hypocotyls prior to hook formation, the question of how auxin asymmetry is established in the early phases of seedling germination remains largely unanswered. Here, we analyzed the auxin distribution and expression of PIN auxin efflux carriers from early phases of germination, and show that bending of the root in response to gravity is the crucial initial cue that governs the hypocotyl bending required for apical hook formation. Importantly, polar auxin transport machinery is established gradually after germination starts as a result of tight root-hypocotyl interaction and a proper balance between abscisic acid and gibberellins."}],"publication_status":"published","citation":{"ista":"Zhu Q, Gallemi M, Pospíšil J, Žádníková P, Strnad M, Benková E. 2019. Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis. Development. 146(17), dev175919.","short":"Q. Zhu, M. Gallemi, J. Pospíšil, P. Žádníková, M. Strnad, E. Benková, Development 146 (2019).","mla":"Zhu, Qiang, et al. “Root Gravity Response Module Guides Differential Growth Determining Both Root Bending and Apical Hook Formation in Arabidopsis.” <i>Development</i>, vol. 146, no. 17, dev175919, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/dev.175919\">10.1242/dev.175919</a>.","ama":"Zhu Q, Gallemi M, Pospíšil J, Žádníková P, Strnad M, Benková E. Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis. <i>Development</i>. 2019;146(17). doi:<a href=\"https://doi.org/10.1242/dev.175919\">10.1242/dev.175919</a>","chicago":"Zhu, Qiang, Marçal Gallemi, Jiří Pospíšil, Petra Žádníková, Miroslav Strnad, and Eva Benková. “Root Gravity Response Module Guides Differential Growth Determining Both Root Bending and Apical Hook Formation in Arabidopsis.” <i>Development</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/dev.175919\">https://doi.org/10.1242/dev.175919</a>.","ieee":"Q. Zhu, M. Gallemi, J. Pospíšil, P. Žádníková, M. Strnad, and E. Benková, “Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis,” <i>Development</i>, vol. 146, no. 17. The Company of Biologists, 2019.","apa":"Zhu, Q., Gallemi, M., Pospíšil, J., Žádníková, P., Strnad, M., &#38; Benková, E. (2019). Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.175919\">https://doi.org/10.1242/dev.175919</a>"}},{"oa":1,"date_updated":"2023-09-13T08:50:57Z","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","_id":"6947","publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","citation":{"chicago":"Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>.","ieee":"F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.","apa":"Assen, F. P. (2019). <i>Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>","short":"F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019.","ista":"Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.","mla":"Assen, Frank P. <i>Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>.","ama":"Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>"},"author":[{"id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","first_name":"Frank P","full_name":"Assen, Frank P","last_name":"Assen","orcid":"0000-0003-3470-6119"}],"abstract":[{"lang":"eng","text":"Lymph nodes  are es s ential organs  of the immune  s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular  cells (FRCs) are  the  main  stromal  cells and  form  a sponge-like extracellular matrix network,   called  conduits ,  which  they   thems elves   enwrap   and  contract.  Lymph,  containing  s oluble  antigens ,  arrive in  lymph  nodes  via afferent lymphatic  vessels that  connect  to  the  s ubcaps ular  s inus   and  conduit  network.  According  to  the  current  paradigm,  the  conduit  network   dis tributes   afferent  lymph  through   lymph  nodes   and  thus   provides   acces s   for  immune  cells to lymph-borne  antigens. An  elas tic  caps ule  s urrounds   the  organ  and  confines   the immune  cells and  FRC  network.   Lymph   nodes   are  completely  packed  with  lymphocytes   and  lymphocyte  numbers  directly  dictates  the size  of  the  organ.  Although  lymphocytes   cons tantly  enter  and  leave  the  lymph  node,  its   s ize  remains   remarkedly   s table  under  homeostatic conditions. It is only partly known  how the cellularity and s ize of the lymph node is regulated and  how  the  lymph  node  is able to swell in inflammation.  The role of the FRC network   in  lymph  node   s welling  and  trans fer  of  fluids   are  inves tigated in  this   thes is.  Furthermore,   we  s tudied  what  trafficking  routes   are  us ed  by  cancer  cells   in  lymph  nodes   to  form  distal metastases.We examined the role of a mechanical feedback in regulation of lymph  node swelling. Using parallel plate compression  and UV-las er  cutting  experiments   we  dis s ected  the  mechanical  force dynamics  of the whole lymph  node, and individually for FRCs  and the  caps ule. Physical forces   generated  by  packed  lymphocytes   directly  affect  the  tens ion  on  the  FRC  network  and  capsule,  which  increases  its  resistance  to   swelling.  This  implies  a  feedback  mechanism  between   tis s ue   pres s ure   and   ability   of   lymphocytes    to   enter   the   organ.   Following   inflammation,  the  lymph  node  swells ∼10 fold in two weeks . Yet, what  is  the role  for tens ion on  the  FRC  network   and  caps ule,  and  how  are  lymphocytes   able  to  enter  in  conditions  that resist swelling remain open ques tions . We s how that tens ion on the FRC network is  important to  limit  the  swelling  rate  of  the  organ  so  that  the  FRC  network  can  grow  in  a  coordinated  fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates  and a dis organized FRC network  in the inflamed lymph  node. Growth  of the FRC network  in  turn  is   expected  to  releas e  tens ion  on  thes e  s tructures   and  lowers   the  res is tance  to  swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of  swelling coincides   with  a  thickening  of  the  caps ule,  which  forms   a  thick  res is tant  band  around  the organ and lowers  tens ion on the FRC network  to form a new force equilibrium.The  FRC  and  conduit   network   are  further   believed  to  be  a  privileged  s ite  of  s oluble  information  within  the  lymph  node,  although  many  details   remain  uns olved.  We  s how  by  3D  ultra-recons truction   that  FRCs   and  antigen  pres enting  cells   cover  the  s urface  of  conduit  s ys tem for more  than 99% and we dis cus s  the implications  for s oluble information  exchangeat the conduit level.Finally, there  is an ongoing debate in the cancer field whether and how cancer cells  in lymph nodes   s eed  dis tal  metas tas es .  We  s how  that  cancer  cells   infus ed  into  the  lymph  node  can  utilize trafficking routes of immune  cells and  rapidly  migrate  to  blood  vessels. Once  in  the  blood circulation,  these cells are able to form  metastases in distal tissues."}],"alternative_title":["ISTA Thesis"],"ddc":["570"],"related_material":{"record":[{"status":"public","id":"664","relation":"part_of_dissertation"},{"status":"public","id":"402","relation":"part_of_dissertation"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"doi":"10.15479/AT:ISTA:6947","year":"2019","title":"Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking","page":"142","file_date_updated":"2020-11-07T23:30:03Z","type":"dissertation","day":"9","status":"public","supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K","first_name":"Michael K"}],"department":[{"_id":"MiSi"}],"has_accepted_license":"1","degree_awarded":"PhD","date_created":"2019-10-14T16:54:52Z","file":[{"creator":"fassen","file_id":"6990","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"53a739752a500f84d0f8ec953cbbd0b6","date_created":"2019-11-06T12:30:02Z","file_size":214172667,"file_name":"PhDthesis_FrankAssen_revised2.docx","access_level":"closed","date_updated":"2020-11-07T23:30:03Z","embargo_to":"open_access"},{"file_size":83637532,"embargo":"2020-11-06","file_name":"PhDthesis_FrankAssen_revised2.pdf","checksum":"8c156b65d9347bb599623a4b09f15d15","date_created":"2019-11-06T12:30:57Z","access_level":"open_access","date_updated":"2020-11-07T23:30:03Z","relation":"main_file","content_type":"application/pdf","creator":"fassen","file_id":"6991"}],"date_published":"2019-10-09T00:00:00Z","month":"10","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria"},{"article_processing_charge":"No","volume":179,"date_updated":"2024-03-25T23:30:21Z","oa":1,"publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"pmid":1,"_id":"7001","project":[{"grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020"}],"quality_controlled":"1","oa_version":"Submitted Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Schwayer, Cornelia, et al. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” <i>Cell</i>, vol. 179, no. 4, Cell Press, 2019, p. 937–952.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">10.1016/j.cell.2019.10.006</a>.","ama":"Schwayer C, Shamipour S, Pranjic-Ferscha K, et al. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. <i>Cell</i>. 2019;179(4):937-952.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">10.1016/j.cell.2019.10.006</a>","short":"C. Schwayer, S. Shamipour, K. Pranjic-Ferscha, A. Schauer, M. Balda, M. Tada, K. Matter, C.-P.J. Heisenberg, Cell 179 (2019) 937–952.e18.","ista":"Schwayer C, Shamipour S, Pranjic-Ferscha K, Schauer A, Balda M, Tada M, Matter K, Heisenberg C-PJ. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell. 179(4), 937–952.e18.","ieee":"C. Schwayer <i>et al.</i>, “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” <i>Cell</i>, vol. 179, no. 4. Cell Press, p. 937–952.e18, 2019.","apa":"Schwayer, C., Shamipour, S., Pranjic-Ferscha, K., Schauer, A., Balda, M., Tada, M., … Heisenberg, C.-P. J. (2019). Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">https://doi.org/10.1016/j.cell.2019.10.006</a>","chicago":"Schwayer, Cornelia, Shayan Shamipour, Kornelija Pranjic-Ferscha, Alexandra Schauer, M Balda, M Tada, K Matter, and Carl-Philipp J Heisenberg. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” <i>Cell</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">https://doi.org/10.1016/j.cell.2019.10.006</a>."},"publication_status":"published","author":[{"first_name":"Cornelia","orcid":"0000-0001-5130-2226","full_name":"Schwayer, Cornelia","last_name":"Schwayer","id":"3436488C-F248-11E8-B48F-1D18A9856A87"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","full_name":"Shamipour, Shayan","last_name":"Shamipour","first_name":"Shayan"},{"id":"4362B3C2-F248-11E8-B48F-1D18A9856A87","full_name":"Pranjic-Ferscha, Kornelija","last_name":"Pranjic-Ferscha","first_name":"Kornelija"},{"first_name":"Alexandra","full_name":"Schauer, Alexandra","last_name":"Schauer","orcid":"0000-0001-7659-9142","id":"30A536BA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"M","last_name":"Balda","full_name":"Balda, M"},{"full_name":"Tada, M","last_name":"Tada","first_name":"M"},{"first_name":"K","last_name":"Matter","full_name":"Matter, K"},{"orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"related_material":{"link":[{"relation":"press_release","description":"News auf IST Website","url":"https://ist.ac.at/en/news/biochemistry-meets-mechanics-the-sensitive-nature-of-cell-cell-contact-formation-in-embryo-development/"}],"record":[{"status":"public","id":"7186","relation":"dissertation_contains"},{"status":"public","relation":"dissertation_contains","id":"8350"}]},"ddc":["570"],"doi":"10.1016/j.cell.2019.10.006","year":"2019","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"ec_funded":1,"title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","external_id":{"pmid":["31675500"],"isi":["000493898000012"]},"publication":"Cell","issue":"4","file_date_updated":"2020-10-21T07:09:45Z","page":"937-952.e18","day":"31","type":"journal_article","intvolume":"       179","status":"public","has_accepted_license":"1","department":[{"_id":"CaHe"},{"_id":"BjHo"}],"date_created":"2019-11-12T12:51:06Z","file":[{"date_updated":"2020-10-21T07:09:45Z","access_level":"open_access","date_created":"2020-10-21T07:09:45Z","checksum":"33dac4bb77ee630e2666e936b4d57980","file_name":"2019_Cell_Schwayer_accepted.pdf","file_size":8805878,"file_id":"8684","creator":"dernst","content_type":"application/pdf","relation":"main_file","success":1}],"month":"10","date_published":"2019-10-31T00:00:00Z","article_type":"original","scopus_import":"1","publisher":"Cell Press","language":[{"iso":"eng"}]},{"page":"192","file_date_updated":"2020-07-14T12:47:51Z","type":"dissertation","day":"12","status":"public","supervisor":[{"first_name":"Jiří","last_name":"Friml","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"JiFr"}],"has_accepted_license":"1","degree_awarded":"PhD","date_created":"2019-12-11T21:24:39Z","file":[{"access_level":"closed","date_updated":"2020-07-14T12:47:51Z","checksum":"ef981c1a3b1d9da0edcbedcff4970d37","date_created":"2019-12-12T09:32:36Z","file_size":20454014,"file_name":"Thesis_Mina_final_upload_7.docx","file_id":"7175","creator":"mvasilev","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"},{"access_level":"open_access","date_updated":"2020-07-14T12:47:51Z","checksum":"3882c4585e46c9cfb486e4225cad54ab","date_created":"2019-12-12T09:33:10Z","file_size":11565025,"file_name":"Thesis_Mina_final_upload_7.pdf","creator":"mvasilev","file_id":"7176","relation":"main_file","content_type":"application/pdf"}],"date_published":"2019-12-12T00:00:00Z","month":"12","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","date_updated":"2025-05-07T11:12:29Z","oa":1,"oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"eissn":["2663-337X"]},"_id":"7172","citation":{"ieee":"M. K. Vasileva, “Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana,” Institute of Science and Technology Austria, 2019.","apa":"Vasileva, M. K. (2019). <i>Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7172\">https://doi.org/10.15479/AT:ISTA:7172</a>","chicago":"Vasileva, Mina K. “Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:7172\">https://doi.org/10.15479/AT:ISTA:7172</a>.","ama":"Vasileva MK. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7172\">10.15479/AT:ISTA:7172</a>","mla":"Vasileva, Mina K. <i>Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7172\">10.15479/AT:ISTA:7172</a>.","short":"M.K. Vasileva, Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana, Institute of Science and Technology Austria, 2019.","ista":"Vasileva MK. 2019. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. Institute of Science and Technology Austria."},"publication_status":"published","author":[{"last_name":"Vasileva","full_name":"Vasileva, Mina K","first_name":"Mina K","id":"3407EB18-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"lang":"eng","text":"The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers.\r\nThe first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone.\r\nThe second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition.\r\nThe third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24.\r\nIn the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis.\r\nIn the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results.\r\nIn the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes."}],"alternative_title":["ISTA Thesis"],"ddc":["570"],"related_material":{"record":[{"relation":"part_of_dissertation","id":"6377","status":"public"},{"id":"449","relation":"part_of_dissertation","status":"public"},{"status":"public","id":"1346","relation":"part_of_dissertation"}]},"year":"2019","doi":"10.15479/AT:ISTA:7172","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"title":"Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana"},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"SSU"}],"year":"2019","doi":"10.15479/AT:ISTA:7186","title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","alternative_title":["ISTA Thesis"],"related_material":{"record":[{"relation":"dissertation_contains","id":"1096","status":"public"},{"status":"public","id":"7001","relation":"part_of_dissertation"}]},"ddc":["570"],"publication_status":"published","citation":{"ama":"Schwayer C. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7186\">10.15479/AT:ISTA:7186</a>","mla":"Schwayer, Cornelia. <i>Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7186\">10.15479/AT:ISTA:7186</a>.","ista":"Schwayer C. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Institute of Science and Technology Austria.","short":"C. Schwayer, Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow, Institute of Science and Technology Austria, 2019.","apa":"Schwayer, C. (2019). <i>Mechanosensation of tight junctions depends on ZO-1 phase separation and flow</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7186\">https://doi.org/10.15479/AT:ISTA:7186</a>","ieee":"C. Schwayer, “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” Institute of Science and Technology Austria, 2019.","chicago":"Schwayer, Cornelia. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:7186\">https://doi.org/10.15479/AT:ISTA:7186</a>."},"abstract":[{"text":"Tissue morphogenesis in developmental or physiological processes is regulated by molecular\r\nand mechanical signals. While the molecular signaling cascades are increasingly well\r\ndescribed, the mechanical signals affecting tissue shape changes have only recently been\r\nstudied in greater detail. To gain more insight into the mechanochemical and biophysical\r\nbasis of an epithelial spreading process (epiboly) in early zebrafish development, we studied\r\ncell-cell junction formation and actomyosin network dynamics at the boundary between\r\nsurface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly,\r\nthe cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of\r\ngastrulation. It has been previously shown that an actomyosin ring residing within the YSL\r\npulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby\r\ndragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL\r\nactomyosin ring to EVL cells; however, the nature and formation of the junctional structure\r\nmediating this process has not been well described so far. Therefore, our main aim was to\r\ndetermine the nature, dynamics and potential function of the EVL-YSL junction during this\r\nepithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a\r\nmechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process\r\nof TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated\r\nZonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we\r\ncould demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk\r\ncell, and ZO-1 undergoes a phase separation process that likely renders the protein\r\nresponsive to flows. These flows are directed towards the junction and mediate proper\r\ntension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets\r\nincorporated into the junctional pool mediated through its direct actin-binding domain.\r\nWhen the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their\r\nproper mechanosensitive responses resulting in slower tissue spreading. We could further\r\ndemonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin\r\nring formation. This suggests that a mechanochemical feedback loop is at work during\r\nzebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin\r\ncontractility and flows positively influence ZO-1 junctional recruitment. Finally, such a\r\nmesoscale polarization process mediated through the flow of phase-separated protein\r\nclusters might have implications for other processes such as immunological synapse\r\nformation, C. elegans zygote polarization and wound healing.","lang":"eng"}],"author":[{"id":"3436488C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwayer, Cornelia","last_name":"Schwayer","orcid":"0000-0001-5130-2226","first_name":"Cornelia"}],"date_updated":"2023-09-07T12:56:42Z","oa":1,"article_processing_charge":"No","_id":"7186","publication_identifier":{"issn":["2663-337X"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","month":"12","date_published":"2019-12-16T00:00:00Z","publisher":"Institute of Science and Technology Austria","language":[{"iso":"eng"}],"has_accepted_license":"1","degree_awarded":"PhD","department":[{"_id":"CaHe"}],"file":[{"relation":"source_file","content_type":"application/zip","creator":"cschwayer","file_id":"7194","file_size":19431292,"file_name":"DocumentSourceFiles.zip","checksum":"585583c1c875c5d9525703a539668a7c","date_created":"2019-12-19T15:18:11Z","access_level":"closed","date_updated":"2020-07-14T12:47:52Z"},{"relation":"main_file","content_type":"application/pdf","creator":"cschwayer","file_id":"7195","access_level":"open_access","date_updated":"2020-07-14T12:47:52Z","file_size":19226428,"file_name":"Thesis_CS_final.pdf","checksum":"9b9b24351514948d27cec659e632e2cd","date_created":"2019-12-19T15:19:21Z"}],"date_created":"2019-12-16T14:26:14Z","day":"16","type":"dissertation","supervisor":[{"first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"status":"public","page":"107","file_date_updated":"2020-07-14T12:47:52Z"},{"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"5744","isi":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"8358","status":"public"}]},"ddc":["570"],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"year":"2019","doi":"10.1038/s41467-019-13702-4","ec_funded":1,"external_id":{"isi":["000503009300001"]},"title":"Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA","volume":10,"oa":1,"date_updated":"2023-09-07T13:18:51Z","article_processing_charge":"No","_id":"7197","publication_identifier":{"issn":["2041-1723"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","quality_controlled":"1","project":[{"grant_number":"679239","call_identifier":"H2020","_id":"2595697A-B435-11E9-9278-68D0E5697425","name":"Self-Organization of the Bacterial Cell"},{"name":"Reconstitution of Bacterial Cell Division Using Purified Components","_id":"260D98C8-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","publication_status":"published","citation":{"ieee":"P. R. Dos Santos Caldas, M. D. Lopez Pelegrin, D. J. G. Pearce, N. B. Budanur, J. Brugués, and M. Loose, “Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA,” <i>Nature Communications</i>, vol. 10. Springer Nature, 2019.","apa":"Dos Santos Caldas, P. R., Lopez Pelegrin, M. D., Pearce, D. J. G., Budanur, N. B., Brugués, J., &#38; Loose, M. (2019). Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-019-13702-4\">https://doi.org/10.1038/s41467-019-13702-4</a>","chicago":"Dos Santos Caldas, Paulo R, Maria D Lopez Pelegrin, Daniel J. G. Pearce, Nazmi B Budanur, Jan Brugués, and Martin Loose. “Cooperative Ordering of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinker ZapA.” <i>Nature Communications</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41467-019-13702-4\">https://doi.org/10.1038/s41467-019-13702-4</a>.","ama":"Dos Santos Caldas PR, Lopez Pelegrin MD, Pearce DJG, Budanur NB, Brugués J, Loose M. Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. <i>Nature Communications</i>. 2019;10. doi:<a href=\"https://doi.org/10.1038/s41467-019-13702-4\">10.1038/s41467-019-13702-4</a>","mla":"Dos Santos Caldas, Paulo R., et al. “Cooperative Ordering of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinker ZapA.” <i>Nature Communications</i>, vol. 10, 5744, Springer Nature, 2019, doi:<a href=\"https://doi.org/10.1038/s41467-019-13702-4\">10.1038/s41467-019-13702-4</a>.","ista":"Dos Santos Caldas PR, Lopez Pelegrin MD, Pearce DJG, Budanur NB, Brugués J, Loose M. 2019. Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. Nature Communications. 10, 5744.","short":"P.R. Dos Santos Caldas, M.D. Lopez Pelegrin, D.J.G. Pearce, N.B. Budanur, J. Brugués, M. Loose, Nature Communications 10 (2019)."},"abstract":[{"lang":"eng","text":"During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner."}],"author":[{"orcid":"0000-0001-6730-4461","last_name":"Dos Santos Caldas","full_name":"Dos Santos Caldas, Paulo R","first_name":"Paulo R","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87"},{"id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","first_name":"Maria D","last_name":"Lopez Pelegrin","full_name":"Lopez Pelegrin, Maria D"},{"first_name":"Daniel J. G.","full_name":"Pearce, Daniel J. G.","last_name":"Pearce"},{"id":"3EA1010E-F248-11E8-B48F-1D18A9856A87","last_name":"Budanur","full_name":"Budanur, Nazmi B","orcid":"0000-0003-0423-5010","first_name":"Nazmi B"},{"first_name":"Jan","last_name":"Brugués","full_name":"Brugués, Jan"},{"first_name":"Martin","full_name":"Loose, Martin","last_name":"Loose","orcid":"0000-0001-7309-9724","id":"462D4284-F248-11E8-B48F-1D18A9856A87"}],"has_accepted_license":"1","department":[{"_id":"MaLo"},{"_id":"BjHo"}],"date_created":"2019-12-20T12:22:57Z","file":[{"checksum":"a1b44b427ba341383197790d0e8789fa","date_created":"2019-12-23T07:34:56Z","file_size":8488733,"file_name":"2019_NatureComm_Caldas.pdf","access_level":"open_access","date_updated":"2020-07-14T12:47:53Z","file_id":"7208","creator":"dernst","relation":"main_file","content_type":"application/pdf"}],"month":"12","date_published":"2019-12-17T00:00:00Z","article_type":"original","publisher":"Springer Nature","scopus_import":"1","language":[{"iso":"eng"}],"publication":"Nature Communications","file_date_updated":"2020-07-14T12:47:53Z","day":"17","type":"journal_article","intvolume":"        10","status":"public"},{"abstract":[{"text":"Background\r\nSynaptic vesicles (SVs) are an integral part of the neurotransmission machinery, and isolation of SVs from their host neuron is necessary to reveal their most fundamental biochemical and functional properties in in vitro assays. Isolated SVs from neurons that have been genetically engineered, e.g. to introduce genetically encoded indicators, are not readily available but would permit new insights into SV structure and function. Furthermore, it is unclear if cultured neurons can provide sufficient starting material for SV isolation procedures.\r\n\r\nNew method\r\nHere, we demonstrate an efficient ex vivo procedure to obtain functional SVs from cultured rat cortical neurons after genetic engineering with a lentivirus.\r\n\r\nResults\r\nWe show that ∼108 plated cortical neurons allow isolation of suitable SV amounts for functional analysis and imaging. We found that SVs isolated from cultured neurons have neurotransmitter uptake comparable to that of SVs isolated from intact cortex. Using total internal reflection fluorescence (TIRF) microscopy, we visualized an exogenous SV-targeted marker protein and demonstrated the high efficiency of SV modification.\r\n\r\nComparison with existing methods\r\nObtaining SVs from genetically engineered neurons currently generally requires the availability of transgenic animals, which is constrained by technical (e.g. cost and time) and biological (e.g. developmental defects and lethality) limitations.\r\n\r\nConclusions\r\nThese results demonstrate the modification and isolation of functional SVs using cultured neurons and viral transduction. The ability to readily obtain SVs from genetically engineered neurons will permit linking in situ studies to in vitro experiments in a variety of genetic contexts.","lang":"eng"}],"author":[{"first_name":"Catherine","last_name":"Mckenzie","full_name":"Mckenzie, Catherine","id":"3EEDE19A-F248-11E8-B48F-1D18A9856A87"},{"id":"44A924DC-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslava","last_name":"Spanova","full_name":"Spanova, Miroslava"},{"id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2739-8843","full_name":"Johnson, Alexander J","last_name":"Johnson","first_name":"Alexander J"},{"full_name":"Kainrath, Stephanie","last_name":"Kainrath","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87"},{"id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa","orcid":"0000-0002-9438-4783","full_name":"Zheden, Vanessa","last_name":"Zheden"},{"first_name":"Harald H.","full_name":"Sitte, Harald H.","last_name":"Sitte"},{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L","full_name":"Janovjak, Harald L","last_name":"Janovjak","orcid":"0000-0002-8023-9315"}],"publication_status":"published","citation":{"ama":"Mckenzie C, Spanova M, Johnson AJ, et al. Isolation of synaptic vesicles from genetically engineered cultured neurons. <i>Journal of Neuroscience Methods</i>. 2019;312:114-121. doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2018.11.018\">10.1016/j.jneumeth.2018.11.018</a>","mla":"Mckenzie, Catherine, et al. “Isolation of Synaptic Vesicles from Genetically Engineered Cultured Neurons.” <i>Journal of Neuroscience Methods</i>, vol. 312, Elsevier, 2019, pp. 114–21, doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2018.11.018\">10.1016/j.jneumeth.2018.11.018</a>.","ista":"Mckenzie C, Spanova M, Johnson AJ, Kainrath S, Zheden V, Sitte HH, Janovjak HL. 2019. Isolation of synaptic vesicles from genetically engineered cultured neurons. Journal of Neuroscience Methods. 312, 114–121.","short":"C. Mckenzie, M. Spanova, A.J. Johnson, S. Kainrath, V. Zheden, H.H. Sitte, H.L. Janovjak, Journal of Neuroscience Methods 312 (2019) 114–121.","apa":"Mckenzie, C., Spanova, M., Johnson, A. J., Kainrath, S., Zheden, V., Sitte, H. H., &#38; Janovjak, H. L. (2019). Isolation of synaptic vesicles from genetically engineered cultured neurons. <i>Journal of Neuroscience Methods</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jneumeth.2018.11.018\">https://doi.org/10.1016/j.jneumeth.2018.11.018</a>","ieee":"C. Mckenzie <i>et al.</i>, “Isolation of synaptic vesicles from genetically engineered cultured neurons,” <i>Journal of Neuroscience Methods</i>, vol. 312. Elsevier, pp. 114–121, 2019.","chicago":"Mckenzie, Catherine, Miroslava Spanova, Alexander J Johnson, Stephanie Kainrath, Vanessa Zheden, Harald H. Sitte, and Harald L Janovjak. “Isolation of Synaptic Vesicles from Genetically Engineered Cultured Neurons.” <i>Journal of Neuroscience Methods</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.jneumeth.2018.11.018\">https://doi.org/10.1016/j.jneumeth.2018.11.018</a>."},"pmid":1,"_id":"7406","publication_identifier":{"issn":["0165-0270"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"None","project":[{"_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7","grant_number":"303564"},{"call_identifier":"FWF","_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants","grant_number":"I03630"},{"name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24"}],"quality_controlled":"1","volume":312,"date_updated":"2023-09-06T15:27:29Z","article_processing_charge":"No","title":"Isolation of synaptic vesicles from genetically engineered cultured neurons","external_id":{"pmid":["30496761"],"isi":["000456220900013"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"}],"doi":"10.1016/j.jneumeth.2018.11.018","year":"2019","ec_funded":1,"isi":1,"intvolume":"       312","status":"public","day":"15","type":"journal_article","publication":"Journal of Neuroscience Methods","page":"114-121","publisher":"Elsevier","scopus_import":"1","language":[{"iso":"eng"}],"month":"01","date_published":"2019-01-15T00:00:00Z","article_type":"original","date_created":"2020-01-30T09:12:19Z","department":[{"_id":"HaJa"},{"_id":"Bio"}]},{"day":"01","type":"journal_article","intvolume":"        21","status":"public","publication":"Nature Cell Biology","page":"169–178","file_date_updated":"2020-10-21T07:18:35Z","month":"02","date_published":"2019-02-01T00:00:00Z","article_type":"original","scopus_import":"1","publisher":"Nature Publishing Group","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"file":[{"file_name":"2018_NatureCellBio_Petridou_accepted.pdf","file_size":71590590,"date_created":"2020-10-21T07:18:35Z","checksum":"e38523787b3bc84006f2793de99ad70f","date_updated":"2020-10-21T07:18:35Z","access_level":"open_access","success":1,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_id":"8685"}],"date_created":"2018-12-30T22:59:15Z","citation":{"short":"N. Petridou, S. Grigolon, G. Salbreux, E.B. Hannezo, C.-P.J. Heisenberg, Nature Cell Biology 21 (2019) 169–178.","ista":"Petridou N, Grigolon S, Salbreux G, Hannezo EB, Heisenberg C-PJ. 2019. Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling. Nature Cell Biology. 21, 169–178.","mla":"Petridou, Nicoletta, et al. “Fluidization-Mediated Tissue Spreading by Mitotic Cell Rounding and Non-Canonical Wnt Signalling.” <i>Nature Cell Biology</i>, vol. 21, Nature Publishing Group, 2019, pp. 169–178, doi:<a href=\"https://doi.org/10.1038/s41556-018-0247-4\">10.1038/s41556-018-0247-4</a>.","ama":"Petridou N, Grigolon S, Salbreux G, Hannezo EB, Heisenberg C-PJ. Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling. <i>Nature Cell Biology</i>. 2019;21:169–178. doi:<a href=\"https://doi.org/10.1038/s41556-018-0247-4\">10.1038/s41556-018-0247-4</a>","chicago":"Petridou, Nicoletta, Silvia Grigolon, Guillaume Salbreux, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Fluidization-Mediated Tissue Spreading by Mitotic Cell Rounding and Non-Canonical Wnt Signalling.” <i>Nature Cell Biology</i>. Nature Publishing Group, 2019. <a href=\"https://doi.org/10.1038/s41556-018-0247-4\">https://doi.org/10.1038/s41556-018-0247-4</a>.","ieee":"N. Petridou, S. Grigolon, G. Salbreux, E. B. Hannezo, and C.-P. J. Heisenberg, “Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling,” <i>Nature Cell Biology</i>, vol. 21. Nature Publishing Group, pp. 169–178, 2019.","apa":"Petridou, N., Grigolon, S., Salbreux, G., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2019). Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling. <i>Nature Cell Biology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41556-018-0247-4\">https://doi.org/10.1038/s41556-018-0247-4</a>"},"publication_status":"published","abstract":[{"lang":"eng","text":"Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell–cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis."}],"author":[{"orcid":"0000-0002-8451-1195","last_name":"Petridou","full_name":"Petridou, Nicoletta","first_name":"Nicoletta","id":"2A003F6C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Silvia","full_name":"Grigolon, Silvia","last_name":"Grigolon"},{"last_name":"Salbreux","full_name":"Salbreux, Guillaume","first_name":"Guillaume"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J"}],"article_processing_charge":"No","volume":21,"oa":1,"date_updated":"2023-09-11T14:03:28Z","publication_identifier":{"issn":["14657392"]},"_id":"5789","pmid":1,"oa_version":"Submitted Version","project":[{"call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"},{"grant_number":"ALTF710-2016","name":"Molecular mechanism of auxindriven formative divisions delineating lateral root organogenesis in plants (EMBO fellowship)","_id":"253E54C8-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2019","doi":"10.1038/s41556-018-0247-4","acknowledged_ssus":[{"_id":"Bio"}],"ec_funded":1,"title":"Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling","external_id":{"isi":["000457468300011"],"pmid":["30559456"]},"isi":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/when-a-fish-becomes-fluid/","relation":"press_release","description":"News on IST Homepage"}]},"ddc":["570"]},{"article_number":"e42093","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2019","doi":"10.7554/eLife.42093","title":"Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration","external_id":{"isi":["000458025300001"]},"volume":8,"oa":1,"date_updated":"2023-08-24T14:46:01Z","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","oa_version":"Published Version","project":[{"grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"_id":"6025","publication_status":"published","citation":{"mla":"Capek, Daniel, et al. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” <i>ELife</i>, vol. 8, e42093, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.42093\">10.7554/eLife.42093</a>.","ama":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.42093\">10.7554/eLife.42093</a>","short":"D. Capek, M. Smutny, A.M. Tichy, M. Morri, H.L. Janovjak, C.-P.J. Heisenberg, ELife 8 (2019).","ista":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. 2019. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. eLife. 8, e42093.","apa":"Capek, D., Smutny, M., Tichy, A. M., Morri, M., Janovjak, H. L., &#38; Heisenberg, C.-P. J. (2019). Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.42093\">https://doi.org/10.7554/eLife.42093</a>","ieee":"D. Capek, M. Smutny, A. M. Tichy, M. Morri, H. L. Janovjak, and C.-P. J. Heisenberg, “Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","chicago":"Capek, Daniel, Michael Smutny, Alexandra Madelaine Tichy, Maurizio Morri, Harald L Janovjak, and Carl-Philipp J Heisenberg. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.42093\">https://doi.org/10.7554/eLife.42093</a>."},"author":[{"id":"31C42484-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5199-9940","full_name":"Capek, Daniel","last_name":"Capek","first_name":"Daniel"},{"full_name":"Smutny, Michael","last_name":"Smutny","orcid":"0000-0002-5920-9090","first_name":"Michael","id":"3FE6E4E8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexandra Madelaine","last_name":"Tichy","full_name":"Tichy, Alexandra Madelaine"},{"id":"4863116E-F248-11E8-B48F-1D18A9856A87","first_name":"Maurizio","last_name":"Morri","full_name":"Morri, Maurizio"},{"first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg"}],"abstract":[{"text":"Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.","lang":"eng"}],"department":[{"_id":"CaHe"},{"_id":"HaJa"}],"has_accepted_license":"1","file":[{"date_updated":"2020-07-14T12:47:17Z","access_level":"open_access","date_created":"2019-02-18T15:17:21Z","checksum":"6cb4ca6d4aa96f6f187a5983aa3e660a","file_name":"2019_elife_Capek.pdf","file_size":5500707,"creator":"dernst","file_id":"6041","content_type":"application/pdf","relation":"main_file"}],"date_created":"2019-02-17T22:59:22Z","date_published":"2019-02-06T00:00:00Z","month":"02","language":[{"iso":"eng"}],"publisher":"eLife Sciences Publications","scopus_import":"1","file_date_updated":"2020-07-14T12:47:17Z","publication":"eLife","type":"journal_article","day":"06","status":"public","intvolume":"         8"},{"issue":"2","publication":"Molecular systems biology","day":"14","type":"journal_article","intvolume":"        15","status":"public","department":[{"_id":"GaTk"}],"date_created":"2019-02-24T22:59:18Z","month":"02","date_published":"2019-02-14T00:00:00Z","publisher":"Embo Press","scopus_import":"1","language":[{"iso":"eng"}],"oa":1,"volume":15,"date_updated":"2023-08-24T14:49:53Z","article_processing_charge":"No","_id":"6046","pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","grant_number":"P27201-B22"},{"_id":"25EB3A80-B435-11E9-9278-68D0E5697425","name":"Revealing the fundamental limits of cell growth","grant_number":"RGP0042/2013"}],"quality_controlled":"1","oa_version":"Submitted Version","publication_status":"published","citation":{"mla":"Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular Systems Biology</i>, vol. 15, no. 2, e8470, Embo Press, 2019, doi:<a href=\"https://doi.org/10.15252/msb.20188470\">10.15252/msb.20188470</a>.","ama":"Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex stress responses in individual bacteria. <i>Molecular systems biology</i>. 2019;15(2). doi:<a href=\"https://doi.org/10.15252/msb.20188470\">10.15252/msb.20188470</a>","ista":"Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of complex stress responses in individual bacteria. Molecular systems biology. 15(2), e8470.","short":"K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).","apa":"Mitosch, K., Rieckh, G., &#38; Bollenbach, M. T. (2019). Temporal order and precision of complex stress responses in individual bacteria. <i>Molecular Systems Biology</i>. Embo Press. <a href=\"https://doi.org/10.15252/msb.20188470\">https://doi.org/10.15252/msb.20188470</a>","ieee":"K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision of complex stress responses in individual bacteria,” <i>Molecular systems biology</i>, vol. 15, no. 2. Embo Press, 2019.","chicago":"Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular Systems Biology</i>. Embo Press, 2019. <a href=\"https://doi.org/10.15252/msb.20188470\">https://doi.org/10.15252/msb.20188470</a>."},"abstract":[{"text":"Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses.","lang":"eng"}],"author":[{"last_name":"Mitosch","full_name":"Mitosch, Karin","first_name":"Karin","id":"39B66846-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Rieckh","full_name":"Rieckh, Georg","first_name":"Georg","id":"34DA8BD6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mark Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/30765425","open_access":"1"}],"article_number":"e8470","acknowledged_ssus":[{"_id":"Bio"}],"year":"2019","doi":"10.15252/msb.20188470","title":"Temporal order and precision of complex stress responses in individual bacteria","external_id":{"pmid":["30765425"],"isi":["000459628300003"]}},{"main_file_link":[{"url":"https://doi.org/10.1016/j.cell.2019.01.019","open_access":"1"}],"isi":1,"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/in-zebrafish-eggs-most-rapidly-growing-cell-inhibits-its-neighbours-through-mechanical-signals/"}]},"doi":"10.1016/j.cell.2019.01.019","year":"2019","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"ec_funded":1,"title":"Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity","external_id":{"pmid":["30773315"],"isi":["000460509600013"]},"article_processing_charge":"No","date_updated":"2023-08-25T08:02:23Z","oa":1,"volume":176,"_id":"6087","pmid":1,"quality_controlled":"1","oa_version":"Published Version","project":[{"grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020"}],"acknowledgement":"We thank Roland Dosch, Makoto Furutani-Seiki, Brian Link, Mary Mullins, and Masazumi Tada for providing transgenic and/or mutant zebrafish lines; Alexandra Schauer, Shayan Shami-Pour, and the rest of the Heisenberg lab for technical assistance and feedback on the manuscript; and the Bioimaging, Electron Microscopy, and Zebrafish facilities of IST Austria for continuous support. This work was supported by an ERC advanced grant ( MECSPEC to C.-P.H.).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Xia, Peng, Daniel J Gütl, Vanessa Zheden, and Carl-Philipp J Heisenberg. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” <i>Cell</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">https://doi.org/10.1016/j.cell.2019.01.019</a>.","ieee":"P. Xia, D. J. Gütl, V. Zheden, and C.-P. J. Heisenberg, “Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity,” <i>Cell</i>, vol. 176, no. 6. Elsevier, p. 1379–1392.e14, 2019.","apa":"Xia, P., Gütl, D. J., Zheden, V., &#38; Heisenberg, C.-P. J. (2019). Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">https://doi.org/10.1016/j.cell.2019.01.019</a>","short":"P. Xia, D.J. Gütl, V. Zheden, C.-P.J. Heisenberg, Cell 176 (2019) 1379–1392.e14.","ista":"Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. 2019. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. 176(6), 1379–1392.e14.","ama":"Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. <i>Cell</i>. 2019;176(6):1379-1392.e14. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">10.1016/j.cell.2019.01.019</a>","mla":"Xia, Peng, et al. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” <i>Cell</i>, vol. 176, no. 6, Elsevier, 2019, p. 1379–1392.e14, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">10.1016/j.cell.2019.01.019</a>."},"publication_status":"published","abstract":[{"lang":"eng","text":"Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. Conversely, MPC specification is defective in taz−/− follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity."}],"author":[{"last_name":"Xia","full_name":"Xia, Peng","orcid":"0000-0002-5419-7756","first_name":"Peng","id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gütl, Daniel J","last_name":"Gütl","first_name":"Daniel J","id":"381929CE-F248-11E8-B48F-1D18A9856A87"},{"id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","full_name":"Zheden, Vanessa","last_name":"Zheden","orcid":"0000-0002-9438-4783","first_name":"Vanessa"},{"orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"CaHe"},{"_id":"EM-Fac"}],"date_created":"2019-03-10T22:59:19Z","month":"03","article_type":"original","date_published":"2019-03-07T00:00:00Z","scopus_import":"1","publisher":"Elsevier","language":[{"iso":"eng"}],"publication":"Cell","issue":"6","page":"1379-1392.e14","day":"07","type":"journal_article","intvolume":"       176","status":"public"}]
