[{"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"The Journal of Experimental Medicine","oa_version":"Published Version","month":"06","file":[{"content_type":"application/pdf","file_name":"2018_rupress_Moalli.pdf","date_updated":"2020-07-14T12:47:32Z","checksum":"86ae5331f9bfced9a6358a790a04bef4","file_size":3841660,"date_created":"2019-05-28T12:40:05Z","creator":"kschuh","file_id":"6498","access_level":"open_access","relation":"main_file"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"type":"journal_article","date_published":"2018-06-06T00:00:00Z","publication_identifier":{"issn":["0022-1007"],"eissn":["1540-9538"]},"oa":1,"quality_controlled":"1","page":"1869–1890","file_date_updated":"2020-07-14T12:47:32Z","publisher":"Rockefeller University Press","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","scopus_import":"1","_id":"6497","issue":"7","author":[{"last_name":"Moalli","first_name":"Federica","full_name":"Moalli, Federica"},{"full_name":"Ficht, Xenia","last_name":"Ficht","first_name":"Xenia"},{"full_name":"Germann, Philipp","first_name":"Philipp","last_name":"Germann"},{"first_name":"Mykhailo","last_name":"Vladymyrov","full_name":"Vladymyrov, Mykhailo"},{"full_name":"Stolp, Bettina","first_name":"Bettina","last_name":"Stolp"},{"full_name":"de Vries, Ingrid","first_name":"Ingrid","last_name":"de Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyck, Ruth","first_name":"Ruth","last_name":"Lyck"},{"full_name":"Balmer, Jasmin","last_name":"Balmer","first_name":"Jasmin"},{"first_name":"Amleto","last_name":"Fiocchi","full_name":"Fiocchi, Amleto"},{"last_name":"Kreutzfeldt","first_name":"Mario","full_name":"Kreutzfeldt, Mario"},{"first_name":"Doron","last_name":"Merkler","full_name":"Merkler, Doron"},{"last_name":"Iannacone","first_name":"Matteo","full_name":"Iannacone, Matteo"},{"full_name":"Ariga, Akitaka","last_name":"Ariga","first_name":"Akitaka"},{"last_name":"Stoffel","first_name":"Michael H.","full_name":"Stoffel, Michael H."},{"full_name":"Sharpe, James","first_name":"James","last_name":"Sharpe"},{"full_name":"Bähler, Martin","last_name":"Bähler","first_name":"Martin"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Diz-Muñoz, Alba","first_name":"Alba","last_name":"Diz-Muñoz"},{"full_name":"Stein, Jens V.","last_name":"Stein","first_name":"Jens V."}],"department":[{"_id":"MiSi"}],"date_created":"2019-05-28T12:36:47Z","article_processing_charge":"No","publication_status":"published","intvolume":"      2015","title":"The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells","volume":2015,"ddc":["570"],"year":"2018","citation":{"apa":"Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I., … Stein, J. V. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1084/jem.20170896\">https://doi.org/10.1084/jem.20170896</a>","ama":"Moalli F, Ficht X, Germann P, et al. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>. 2018;2015(7):1869–1890. doi:<a href=\"https://doi.org/10.1084/jem.20170896\">10.1084/jem.20170896</a>","chicago":"Moalli, Federica, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina Stolp, Ingrid de Vries, Ruth Lyck, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1084/jem.20170896\">https://doi.org/10.1084/jem.20170896</a>.","ieee":"F. Moalli <i>et al.</i>, “The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells,” <i>The Journal of Experimental Medicine</i>, vol. 2015, no. 7. Rockefeller University Press, pp. 1869–1890, 2018.","mla":"Moalli, Federica, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>, vol. 2015, no. 7, Rockefeller University Press, 2018, pp. 1869–1890, doi:<a href=\"https://doi.org/10.1084/jem.20170896\">10.1084/jem.20170896</a>.","short":"F. Moalli, X. Ficht, P. Germann, M. Vladymyrov, B. Stolp, I. de Vries, R. Lyck, J. Balmer, A. Fiocchi, M. Kreutzfeldt, D. Merkler, M. Iannacone, A. Ariga, M.H. Stoffel, J. Sharpe, M. Bähler, M.K. Sixt, A. Diz-Muñoz, J.V. Stein, The Journal of Experimental Medicine 2015 (2018) 1869–1890.","ista":"Moalli F, Ficht X, Germann P, Vladymyrov M, Stolp B, de Vries I, Lyck R, Balmer J, Fiocchi A, Kreutzfeldt M, Merkler D, Iannacone M, Ariga A, Stoffel MH, Sharpe J, Bähler M, Sixt MK, Diz-Muñoz A, Stein JV. 2018. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2015(7), 1869–1890."},"date_updated":"2023-09-19T14:52:08Z","external_id":{"isi":["000440822900011"]},"isi":1,"day":"06","doi":"10.1084/jem.20170896","abstract":[{"lang":"eng","text":"T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations."}]},{"volume":19,"acknowledgement":"This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).","doi":"10.1038/s41590-018-0109-z","day":"18","abstract":[{"lang":"eng","text":"Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux."}],"date_updated":"2024-03-25T23:30:22Z","year":"2018","citation":{"ista":"Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J, Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 19(6), 606–616.","mla":"Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” <i>Nature Immunology</i>, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:<a href=\"https://doi.org/10.1038/s41590-018-0109-z\">10.1038/s41590-018-0109-z</a>.","short":"M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz, J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616.","ieee":"M. Hons <i>et al.</i>, “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” <i>Nature Immunology</i>, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.","chicago":"Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” <i>Nature Immunology</i>. Nature Publishing Group, 2018. <a href=\"https://doi.org/10.1038/s41590-018-0109-z\">https://doi.org/10.1038/s41590-018-0109-z</a>.","apa":"Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J., … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. <i>Nature Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41590-018-0109-z\">https://doi.org/10.1038/s41590-018-0109-z</a>","ama":"Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. <i>Nature Immunology</i>. 2018;19(6):606-616. doi:<a href=\"https://doi.org/10.1038/s41590-018-0109-z\">10.1038/s41590-018-0109-z</a>"},"isi":1,"external_id":{"isi":["000433041500026"],"pmid":["29777221"]},"publisher":"Nature Publishing Group","page":"606 - 616","quality_controlled":"1","ec_funded":1,"publication_status":"published","article_processing_charge":"No","department":[{"_id":"MiSi"},{"_id":"Bio"}],"date_created":"2018-12-11T11:44:10Z","title":"Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells","intvolume":"        19","_id":"15","pmid":1,"scopus_import":"1","author":[{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","last_name":"Hons","first_name":"Miroslav"},{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja","first_name":"Aglaja","last_name":"Kopf"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F"},{"last_name":"Gärtner","first_name":"Florian R","full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Abe, Jun","first_name":"Jun","last_name":"Abe"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","last_name":"Renkawitz","first_name":"Jörg"},{"first_name":"Jens","last_name":"Stein","full_name":"Stein, Jens"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"issue":"6","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/29777221","open_access":"1"}],"status":"public","related_material":{"record":[{"id":"6891","relation":"dissertation_contains","status":"public"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"publist_id":"8040","date_published":"2018-05-18T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"oa_version":"Published Version","project":[{"grant_number":"724373","name":"Cellular navigation along spatial gradients","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"},{"name":"Molecular and system level view of immune cell migration","grant_number":"ALTF 1396-2014","_id":"25A48D24-B435-11E9-9278-68D0E5697425"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"month":"05","publication":"Nature Immunology"},{"date_published":"2018-07-27T00:00:00Z","type":"book_chapter","publication_identifier":{"issn":["0091679X"]},"publist_id":"7768","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication":"Methods in Cell Biology","oa_version":"None","month":"07","language":[{"iso":"eng"}],"date_updated":"2023-09-13T08:56:35Z","year":"2018","citation":{"short":"J. Renkawitz, A. Reversat, A.F. Leithner, J. Merrin, M.K. Sixt, in:, Methods in Cell Biology, Academic Press, 2018, pp. 79–91.","mla":"Renkawitz, Jörg, et al. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” <i>Methods in Cell Biology</i>, vol. 147, Academic Press, 2018, pp. 79–91, doi:<a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">10.1016/bs.mcb.2018.07.004</a>.","ista":"Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. 2018.Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: Methods in Cell Biology. vol. 147, 79–91.","apa":"Renkawitz, J., Reversat, A., Leithner, A. F., Merrin, J., &#38; Sixt, M. K. (2018). Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In <i>Methods in Cell Biology</i> (Vol. 147, pp. 79–91). Academic Press. <a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">https://doi.org/10.1016/bs.mcb.2018.07.004</a>","ama":"Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: <i>Methods in Cell Biology</i>. Vol 147. Academic Press; 2018:79-91. doi:<a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">10.1016/bs.mcb.2018.07.004</a>","ieee":"J. Renkawitz, A. Reversat, A. F. Leithner, J. Merrin, and M. K. Sixt, “Micro-engineered ‘pillar forests’ to study cell migration in complex but controlled 3D environments,” in <i>Methods in Cell Biology</i>, vol. 147, Academic Press, 2018, pp. 79–91.","chicago":"Renkawitz, Jörg, Anne Reversat, Alexander F Leithner, Jack Merrin, and Michael K Sixt. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” In <i>Methods in Cell Biology</i>, 147:79–91. Academic Press, 2018. <a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">https://doi.org/10.1016/bs.mcb.2018.07.004</a>."},"isi":1,"external_id":{"isi":["000452412300006"],"pmid":["30165964"]},"doi":"10.1016/bs.mcb.2018.07.004","day":"27","abstract":[{"lang":"eng","text":"Cells migrating in multicellular organisms steadily traverse complex three-dimensional (3D) environments. To decipher the underlying cell biology, current experimental setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or in vivo environments. While only in vivo experiments are truly physiological, they do not allow for precise manipulation of environmental parameters. 2D in vitro experiments do allow mechanical and chemical manipulations, but increasing evidence demonstrates substantial differences of migratory mechanisms in 2D and 3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate cell migration in complex but fully controllable 3D environments. Pillar forests are polydimethylsiloxane-based setups, in which two closely adjacent surfaces are interconnected by arrays of micrometer-sized pillars. Changing the pillar shape, size, height and the inter-pillar distance precisely manipulates microenvironmental parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily combined with chemotactic cues, surface coatings, diverse cell types and advanced imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration assays with the precise definition of 3D environmental parameters."}],"volume":147,"pmid":1,"_id":"153","scopus_import":"1","author":[{"last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0666-8928","full_name":"Reversat, Anne","first_name":"Anne","last_name":"Reversat","id":"35B76592-F248-11E8-B48F-1D18A9856A87"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","first_name":"Alexander F","last_name":"Leithner"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin","first_name":"Jack"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","department":[{"_id":"MiSi"},{"_id":"NanoFab"}],"date_created":"2018-12-11T11:44:54Z","article_processing_charge":"No","title":"Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments","intvolume":"       147","page":"79 - 91","quality_controlled":"1","publisher":"Academic Press"},{"main_file_link":[{"url":"https://doi.org/10.1126/science.aal3662","open_access":"1"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6947"}]},"type":"journal_article","date_published":"2018-03-23T00:00:00Z","oa":1,"publist_id":"7428","language":[{"iso":"eng"}],"publication":"Science","project":[{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"}],"acknowledged_ssus":[{"_id":"Bio"}],"oa_version":"Published Version","month":"03","acknowledgement":"M.B. was supported by the Cell Communication in Health and Disease graduate study program of the Austrian Science Fund (FWF) and the Medical University of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556) and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging, the Sixt lab for intellectual input, M. Schunn for help with the design of the in vivo experiments, F. Langer for technical assistance with the in vivo experiments, the bioimaging facility of IST Austria for support, and R. Efferl for providing the CT26 cell line.","volume":359,"citation":{"mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>.","short":"M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018) 1408–1411.","ista":"Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382), 1408–1411.","ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. 2018;359(6382):1408-1411. doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>","apa":"Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G., … Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>","ieee":"M. Brown <i>et al.</i>, “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” <i>Science</i>, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","chicago":"Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner, Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>. American Association for the Advancement of Science, 2018. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>."},"year":"2018","date_updated":"2024-03-25T23:30:05Z","external_id":{"isi":["000428043600047"],"pmid":["29567714"]},"isi":1,"day":"23","doi":"10.1126/science.aal3662","abstract":[{"text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.","lang":"eng"}],"ec_funded":1,"quality_controlled":"1","page":"1408 - 1411","publisher":"American Association for the Advancement of Science","article_type":"original","scopus_import":"1","_id":"402","pmid":1,"issue":"6382","author":[{"first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P","first_name":"Frank P","last_name":"Assen","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"full_name":"Schachner, Helga","first_name":"Helga","last_name":"Schachner"},{"first_name":"Gabriele","last_name":"Asfour","full_name":"Asfour, Gabriele"},{"full_name":"Bagó Horváth, Zsuzsanna","first_name":"Zsuzsanna","last_name":"Bagó Horváth"},{"full_name":"Stein, Jens","last_name":"Stein","first_name":"Jens"},{"full_name":"Uhrin, Pavel","last_name":"Uhrin","first_name":"Pavel"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"}],"article_processing_charge":"No","department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:46:16Z","publication_status":"published","intvolume":"       359","title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice"},{"publication":"European Journal of Immunology","has_accepted_license":"1","acknowledged_ssus":[{"_id":"SSU"}],"oa_version":"Published Version","project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients"}],"month":"02","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"date_published":"2018-02-13T00:00:00Z","type":"journal_article","oa":1,"publist_id":"7386","file":[{"file_name":"IST-2018-1067-v1+2_Leithner_et_al-2018-European_Journal_of_Immunology.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:46:27Z","checksum":"9d5b74cd016505aeb9a4c2d33bbedaeb","file_size":590106,"date_created":"2018-12-12T10:13:56Z","creator":"system","file_id":"5044","relation":"main_file","access_level":"open_access"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"437","scopus_import":"1","license":"https://creativecommons.org/licenses/by-nc/4.0/","author":[{"first_name":"Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","first_name":"Jörg","last_name":"Renkawitz","orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries","full_name":"De Vries, Ingrid"},{"last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Haecker, Hans","last_name":"Haecker","first_name":"Hans"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K"}],"issue":"6","publication_status":"published","date_created":"2018-12-11T11:46:28Z","department":[{"_id":"MiSi"},{"_id":"Bio"}],"article_processing_charge":"Yes (via OA deal)","pubrep_id":"1067","title":"Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration","intvolume":"        48","page":"1074 - 1077","ec_funded":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:46:27Z","publisher":"Wiley-Blackwell","date_updated":"2023-09-11T14:01:18Z","citation":{"ista":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. 2018. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. 48(6), 1074–1077.","short":"A.F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, M.K. Sixt, European Journal of Immunology 48 (2018) 1074–1077.","mla":"Leithner, Alexander F., et al. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” <i>European Journal of Immunology</i>, vol. 48, no. 6, Wiley-Blackwell, 2018, pp. 1074–77, doi:<a href=\"https://doi.org/10.1002/eji.201747358\">10.1002/eji.201747358</a>.","chicago":"Leithner, Alexander F, Jörg Renkawitz, Ingrid de Vries, Robert Hauschild, Hans Haecker, and Michael K Sixt. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” <i>European Journal of Immunology</i>. Wiley-Blackwell, 2018. <a href=\"https://doi.org/10.1002/eji.201747358\">https://doi.org/10.1002/eji.201747358</a>.","ieee":"A. F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, and M. K. Sixt, “Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration,” <i>European Journal of Immunology</i>, vol. 48, no. 6. Wiley-Blackwell, pp. 1074–1077, 2018.","ama":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. <i>European Journal of Immunology</i>. 2018;48(6):1074-1077. doi:<a href=\"https://doi.org/10.1002/eji.201747358\">10.1002/eji.201747358</a>","apa":"Leithner, A. F., Renkawitz, J., de Vries, I., Hauschild, R., Haecker, H., &#38; Sixt, M. K. (2018). Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. <i>European Journal of Immunology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/eji.201747358\">https://doi.org/10.1002/eji.201747358</a>"},"year":"2018","isi":1,"external_id":{"isi":["000434963700016"]},"doi":"10.1002/eji.201747358","day":"13","abstract":[{"text":"Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity.","lang":"eng"}],"acknowledgement":"This work was supported by grants of the European Research Council (ERC CoG 724373) and the Austrian Science Fund (FWF) to M.S. We thank the scientific support units at IST Austria for excellent technical support.\r\nWe thank the  scientific  support units at IST Austria for excellent technical support.   ","volume":48,"ddc":["570"]},{"language":[{"iso":"eng"}],"oa_version":"None","month":"01","publication":"Current Biology","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication_identifier":{"issn":["09609822"]},"publist_id":"6197","date_published":"2017-01-09T00:00:00Z","type":"journal_article","publisher":"Cell Press","page":"R24 - R25","quality_controlled":"1","publication_status":"published","department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:50:29Z","article_processing_charge":"No","title":"Cell migration: Making the waves","intvolume":"        27","_id":"1161","scopus_import":"1","author":[{"first_name":"Jan","last_name":"Müller","full_name":"Müller, Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"issue":"1","volume":27,"doi":"10.1016/j.cub.2016.11.035","day":"09","abstract":[{"lang":"eng","text":"Coordinated changes of cell shape are often the result of the excitable, wave-like dynamics of the actin cytoskeleton. New work shows that, in migrating cells, protrusion waves arise from mechanochemical crosstalk between adhesion sites, membrane tension and the actin protrusive machinery."}],"date_updated":"2023-09-20T11:28:19Z","citation":{"apa":"Müller, J., &#38; Sixt, M. K. (2017). Cell migration: Making the waves. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">https://doi.org/10.1016/j.cub.2016.11.035</a>","ama":"Müller J, Sixt MK. Cell migration: Making the waves. <i>Current Biology</i>. 2017;27(1):R24-R25. doi:<a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">10.1016/j.cub.2016.11.035</a>","chicago":"Müller, Jan, and Michael K Sixt. “Cell Migration: Making the Waves.” <i>Current Biology</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">https://doi.org/10.1016/j.cub.2016.11.035</a>.","ieee":"J. Müller and M. K. Sixt, “Cell migration: Making the waves,” <i>Current Biology</i>, vol. 27, no. 1. Cell Press, pp. R24–R25, 2017.","short":"J. Müller, M.K. Sixt, Current Biology 27 (2017) R24–R25.","mla":"Müller, Jan, and Michael K. Sixt. “Cell Migration: Making the Waves.” <i>Current Biology</i>, vol. 27, no. 1, Cell Press, 2017, pp. R24–25, doi:<a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">10.1016/j.cub.2016.11.035</a>.","ista":"Müller J, Sixt MK. 2017. Cell migration: Making the waves. Current Biology. 27(1), R24–R25."},"year":"2017","isi":1,"external_id":{"isi":["000391902500010"]}},{"volume":46,"status":"public","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6947"}]},"publication_identifier":{"issn":["10747613"]},"day":"18","doi":"10.1016/j.immuni.2017.04.006","publist_id":"7065","abstract":[{"text":"Immune cells communicate using cytokine signals, but the quantitative rules of this communication aren't clear. In this issue of Immunity, Oyler-Yaniv et al. (2017) suggest that the distribution of a cytokine within a lymphatic organ is primarily governed by the local density of cells consuming it.","lang":"eng"}],"citation":{"ista":"Assen FP, Sixt MK. 2017. The dynamic cytokine niche. Immunity. 46(4), 519–520.","short":"F.P. Assen, M.K. Sixt, Immunity 46 (2017) 519–520.","mla":"Assen, Frank P., and Michael K. Sixt. “The Dynamic Cytokine Niche.” <i>Immunity</i>, vol. 46, no. 4, Cell Press, 2017, pp. 519–20, doi:<a href=\"https://doi.org/10.1016/j.immuni.2017.04.006\">10.1016/j.immuni.2017.04.006</a>.","chicago":"Assen, Frank P, and Michael K Sixt. “The Dynamic Cytokine Niche.” <i>Immunity</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.immuni.2017.04.006\">https://doi.org/10.1016/j.immuni.2017.04.006</a>.","ieee":"F. P. Assen and M. K. Sixt, “The dynamic cytokine niche,” <i>Immunity</i>, vol. 46, no. 4. Cell Press, pp. 519–520, 2017.","apa":"Assen, F. P., &#38; Sixt, M. K. (2017). The dynamic cytokine niche. <i>Immunity</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.immuni.2017.04.006\">https://doi.org/10.1016/j.immuni.2017.04.006</a>","ama":"Assen FP, Sixt MK. The dynamic cytokine niche. <i>Immunity</i>. 2017;46(4):519-520. doi:<a href=\"https://doi.org/10.1016/j.immuni.2017.04.006\">10.1016/j.immuni.2017.04.006</a>"},"year":"2017","date_updated":"2024-03-25T23:30:05Z","type":"journal_article","date_published":"2017-04-18T00:00:00Z","publisher":"Cell Press","quality_controlled":"1","page":"519 - 520","language":[{"iso":"eng"}],"date_created":"2018-12-11T11:47:47Z","department":[{"_id":"MiSi"}],"publication_status":"published","oa_version":"None","intvolume":"        46","title":"The dynamic cytokine niche","month":"04","scopus_import":1,"_id":"664","publication":"Immunity","issue":"4","author":[{"orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P","first_name":"Frank P","last_name":"Assen","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}]},{"volume":292,"ddc":["570"],"doi":"10.1074/jbc.M116.766923","day":"28","abstract":[{"text":"Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.","lang":"eng"}],"date_updated":"2021-01-12T08:08:34Z","citation":{"ista":"Horsthemke M, Bachg A, Groll K, Moyzio S, Müther B, Hemkemeyer S, Wedlich Söldner R, Sixt MK, Tacke S, Bähler M, Hanley P. 2017. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. Journal of Biological Chemistry. 292(17), 7258–7273.","mla":"Horsthemke, Markus, et al. “Multiple Roles of Filopodial Dynamics in Particle Capture and Phagocytosis and Phenotypes of Cdc42 and Myo10 Deletion.” <i>Journal of Biological Chemistry</i>, vol. 292, no. 17, American Society for Biochemistry and Molecular Biology, 2017, pp. 7258–73, doi:<a href=\"https://doi.org/10.1074/jbc.M116.766923\">10.1074/jbc.M116.766923</a>.","short":"M. Horsthemke, A. Bachg, K. Groll, S. Moyzio, B. Müther, S. Hemkemeyer, R. Wedlich Söldner, M.K. Sixt, S. Tacke, M. Bähler, P. Hanley, Journal of Biological Chemistry 292 (2017) 7258–7273.","chicago":"Horsthemke, Markus, Anne Bachg, Katharina Groll, Sven Moyzio, Barbara Müther, Sandra Hemkemeyer, Roland Wedlich Söldner, et al. “Multiple Roles of Filopodial Dynamics in Particle Capture and Phagocytosis and Phenotypes of Cdc42 and Myo10 Deletion.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2017. <a href=\"https://doi.org/10.1074/jbc.M116.766923\">https://doi.org/10.1074/jbc.M116.766923</a>.","ieee":"M. Horsthemke <i>et al.</i>, “Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion,” <i>Journal of Biological Chemistry</i>, vol. 292, no. 17. American Society for Biochemistry and Molecular Biology, pp. 7258–7273, 2017.","apa":"Horsthemke, M., Bachg, A., Groll, K., Moyzio, S., Müther, B., Hemkemeyer, S., … Hanley, P. (2017). Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M116.766923\">https://doi.org/10.1074/jbc.M116.766923</a>","ama":"Horsthemke M, Bachg A, Groll K, et al. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. <i>Journal of Biological Chemistry</i>. 2017;292(17):7258-7273. doi:<a href=\"https://doi.org/10.1074/jbc.M116.766923\">10.1074/jbc.M116.766923</a>"},"year":"2017","publisher":"American Society for Biochemistry and Molecular Biology","article_type":"original","page":"7258 - 7273","quality_controlled":"1","file_date_updated":"2020-07-14T12:47:37Z","publication_status":"published","department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:47:49Z","title":"Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion","intvolume":"       292","_id":"668","scopus_import":1,"author":[{"full_name":"Horsthemke, Markus","last_name":"Horsthemke","first_name":"Markus"},{"first_name":"Anne","last_name":"Bachg","full_name":"Bachg, Anne"},{"first_name":"Katharina","last_name":"Groll","full_name":"Groll, Katharina"},{"first_name":"Sven","last_name":"Moyzio","full_name":"Moyzio, Sven"},{"full_name":"Müther, Barbara","last_name":"Müther","first_name":"Barbara"},{"first_name":"Sandra","last_name":"Hemkemeyer","full_name":"Hemkemeyer, Sandra"},{"full_name":"Wedlich Söldner, Roland","last_name":"Wedlich Söldner","first_name":"Roland"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Tacke, Sebastian","last_name":"Tacke","first_name":"Sebastian"},{"last_name":"Bähler","first_name":"Martin","full_name":"Bähler, Martin"},{"full_name":"Hanley, Peter","last_name":"Hanley","first_name":"Peter"}],"issue":"17","file":[{"access_level":"open_access","relation":"main_file","file_id":"6971","creator":"dernst","date_created":"2019-10-24T15:25:42Z","checksum":"d488162874326a4bb056065fa549dc4a","file_size":5647880,"date_updated":"2020-07-14T12:47:37Z","content_type":"application/pdf","file_name":"2017_JBC_Horsthemke.pdf"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["00219258"]},"oa":1,"publist_id":"7059","date_published":"2017-04-28T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"oa_version":"Published Version","month":"04","publication":"Journal of Biological Chemistry","has_accepted_license":"1"},{"ddc":["570"],"volume":19,"date_updated":"2023-02-23T12:50:09Z","citation":{"ama":"Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. 2017;19(5):902-909. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>","apa":"Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling, M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>","ieee":"K. Vaahtomeri <i>et al.</i>, “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” <i>Cell Reports</i>, vol. 19, no. 5. Cell Press, pp. 902–909, 2017.","chicago":"Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>.","short":"K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling, W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909.","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>.","ista":"Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909."},"year":"2017","abstract":[{"text":"Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.","lang":"eng"}],"doi":"10.1016/j.celrep.2017.04.027","day":"02","file_date_updated":"2020-07-14T12:47:38Z","page":"902 - 909","ec_funded":1,"quality_controlled":"1","publisher":"Cell Press","author":[{"last_name":"Vaahtomeri","first_name":"Kari","full_name":"Vaahtomeri, Kari","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522"},{"last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Leithner","first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"id":"3C23B994-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8599-1226","full_name":"Mehling, Matthias","first_name":"Matthias","last_name":"Mehling"},{"first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"issue":"5","_id":"672","scopus_import":1,"title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","pubrep_id":"900","intvolume":"        19","publication_status":"published","article_processing_charge":"Yes","date_created":"2018-12-11T11:47:50Z","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","file":[{"date_updated":"2020-07-14T12:47:38Z","content_type":"application/pdf","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","date_created":"2018-12-12T10:14:54Z","file_size":2248814,"checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","file_id":"5109","creator":"system","access_level":"open_access","relation":"main_file"}],"date_published":"2017-05-02T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"publist_id":"7052","publication_identifier":{"issn":["22111247"]},"language":[{"iso":"eng"}],"publication":"Cell Reports","has_accepted_license":"1","month":"05","oa_version":"Published Version","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"},{"grant_number":"Y 564-B12","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}]},{"language":[{"iso":"eng"}],"month":"05","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"oa_version":"None","publication":"Current Biology","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","status":"public","publist_id":"7050","publication_identifier":{"issn":["09609822"]},"type":"journal_article","date_published":"2017-05-09T00:00:00Z","publisher":"Cell Press","quality_controlled":"1","ec_funded":1,"page":"1314 - 1325","intvolume":"        27","title":"Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6","date_created":"2018-12-11T11:47:51Z","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"publication_status":"published","issue":"9","author":[{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","last_name":"Schwarz","first_name":"Jan"},{"first_name":"Veronika","last_name":"Bierbaum","full_name":"Bierbaum, Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87"},{"id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","orcid":"0000-0001-7829-3518","last_name":"Vaahtomeri","first_name":"Kari"},{"full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Brown","first_name":"Markus","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries","full_name":"De Vries, Ingrid"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F"},{"id":"35B76592-F248-11E8-B48F-1D18A9856A87","first_name":"Anne","last_name":"Reversat","orcid":"0000-0003-0666-8928","full_name":"Reversat, Anne"},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tarrant","first_name":"Teresa","full_name":"Tarrant, Teresa"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","first_name":"Tobias"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"scopus_import":1,"_id":"674","volume":27,"abstract":[{"text":"Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.","lang":"eng"}],"day":"09","doi":"10.1016/j.cub.2017.04.004","citation":{"ista":"Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325.","mla":"Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” <i>Current Biology</i>, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:<a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">10.1016/j.cub.2017.04.004</a>.","short":"J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries, A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt, Current Biology 27 (2017) 1314–1325.","chicago":"Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” <i>Current Biology</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">https://doi.org/10.1016/j.cub.2017.04.004</a>.","ieee":"J. Schwarz <i>et al.</i>, “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” <i>Current Biology</i>, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.","apa":"Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries, I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">https://doi.org/10.1016/j.cub.2017.04.004</a>","ama":"Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. <i>Current Biology</i>. 2017;27(9):1314-1325. doi:<a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">10.1016/j.cub.2017.04.004</a>"},"year":"2017","date_updated":"2023-02-23T12:50:44Z"},{"citation":{"apa":"Lademann, C., Renkawitz, J., Pfander, B., &#38; Jentsch, S. (2017). The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.051\">https://doi.org/10.1016/j.celrep.2017.04.051</a>","ama":"Lademann C, Renkawitz J, Pfander B, Jentsch S. The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination. <i>Cell Reports</i>. 2017;19(7):1294-1303. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.051\">10.1016/j.celrep.2017.04.051</a>","chicago":"Lademann, Claudio, Jörg Renkawitz, Boris Pfander, and Stefan Jentsch. “The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.051\">https://doi.org/10.1016/j.celrep.2017.04.051</a>.","ieee":"C. Lademann, J. Renkawitz, B. Pfander, and S. Jentsch, “The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination,” <i>Cell Reports</i>, vol. 19, no. 7. Cell Press, pp. 1294–1303, 2017.","mla":"Lademann, Claudio, et al. “The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination.” <i>Cell Reports</i>, vol. 19, no. 7, Cell Press, 2017, pp. 1294–303, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.051\">10.1016/j.celrep.2017.04.051</a>.","short":"C. Lademann, J. Renkawitz, B. Pfander, S. Jentsch, Cell Reports 19 (2017) 1294–1303.","ista":"Lademann C, Renkawitz J, Pfander B, Jentsch S. 2017. The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination. Cell Reports. 19(7), 1294–1303."},"year":"2017","date_updated":"2021-01-12T08:08:57Z","day":"16","doi":"10.1016/j.celrep.2017.04.051","abstract":[{"lang":"eng","text":"The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR—DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR."}],"volume":19,"ddc":["570"],"scopus_import":1,"_id":"677","issue":"7","author":[{"last_name":"Lademann","first_name":"Claudio","full_name":"Lademann, Claudio"},{"full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","last_name":"Renkawitz","first_name":"Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Boris","last_name":"Pfander","full_name":"Pfander, Boris"},{"last_name":"Jentsch","first_name":"Stefan","full_name":"Jentsch, Stefan"}],"department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:47:52Z","publication_status":"published","intvolume":"        19","pubrep_id":"899","title":"The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination","quality_controlled":"1","page":"1294 - 1303","file_date_updated":"2020-07-14T12:47:40Z","publisher":"Cell Press","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","date_published":"2017-05-16T00:00:00Z","publication_identifier":{"issn":["22111247"]},"oa":1,"publist_id":"7046","file":[{"content_type":"application/pdf","file_name":"IST-2017-899-v1+1_1-s2.0-S2211124717305454-main.pdf","date_updated":"2020-07-14T12:47:40Z","file_size":3005610,"checksum":"efc7287d9c6354983cb151880e9ad72a","date_created":"2018-12-12T10:15:48Z","creator":"system","file_id":"5171","relation":"main_file","access_level":"open_access"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","publication":"Cell Reports","oa_version":"Published Version","month":"05","language":[{"iso":"eng"}]},{"language":[{"iso":"eng"}],"project":[{"name":"The biochemical basis of PAR polarization","grant_number":"T00817-B21","_id":"25985A36-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"oa_version":"Submitted Version","month":"06","publication":"The Journal of Clinical Investigation","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451238/"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12401"}]},"publication_identifier":{"issn":["00219738"]},"publist_id":"7038","oa":1,"type":"journal_article","date_published":"2017-06-01T00:00:00Z","publisher":"American Society for Clinical Investigation","quality_controlled":"1","page":"2051 - 2065","department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:47:53Z","publication_status":"published","intvolume":"       127","title":"The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection","scopus_import":1,"_id":"679","pmid":1,"issue":"6","author":[{"full_name":"Ebner, Florian","last_name":"Ebner","first_name":"Florian"},{"full_name":"Sedlyarov, Vitaly","last_name":"Sedlyarov","first_name":"Vitaly"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","first_name":"Saren","last_name":"Tasciyan"},{"first_name":"Masa","last_name":"Ivin","full_name":"Ivin, Masa"},{"last_name":"Kratochvill","first_name":"Franz","full_name":"Kratochvill, Franz"},{"last_name":"Gratz","first_name":"Nina","full_name":"Gratz, Nina"},{"last_name":"Kenner","first_name":"Lukas","full_name":"Kenner, Lukas"},{"full_name":"Villunger, Andreas","first_name":"Andreas","last_name":"Villunger"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kovarik","first_name":"Pavel","full_name":"Kovarik, Pavel"}],"volume":127,"acknowledgement":"This work was supported by grants from the Austrian Science Fund (FWF) (P27538-B21, I1621-B22, and SFB 43, to PK); by funding from the European Union Seventh Framework Programme Marie Curie Initial Training Networks (FP7-PEOPLE-2012-ITN) for the project INBIONET (INfection BIOlogy Training NETwork under grant agreement PITN-GA-2012-316682; and by a joint research cluster initiative of the University of Vienna and the Medical University of Vienna.","day":"01","doi":"10.1172/JCI80631","abstract":[{"lang":"eng","text":"Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection site. In the context of myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment protected mice against lethal soft tissue infection with Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other antiapoptotic B cell leukemia/ lymphoma 2 (Bcl2) family members. Higher Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that posttranscriptional gene regulation by TTP schedules the termination of the antimicrobial engagement of neutrophils. The balancing role of TTP comes at the cost of an increased risk of bacterial infections."}],"citation":{"ieee":"F. Ebner <i>et al.</i>, “The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection,” <i>The Journal of Clinical Investigation</i>, vol. 127, no. 6. American Society for Clinical Investigation, pp. 2051–2065, 2017.","chicago":"Ebner, Florian, Vitaly Sedlyarov, Saren Tasciyan, Masa Ivin, Franz Kratochvill, Nina Gratz, Lukas Kenner, Andreas Villunger, Michael K Sixt, and Pavel Kovarik. “The RNA-Binding Protein Tristetraprolin Schedules Apoptosis of Pathogen-Engaged Neutrophils during Bacterial Infection.” <i>The Journal of Clinical Investigation</i>. American Society for Clinical Investigation, 2017. <a href=\"https://doi.org/10.1172/JCI80631\">https://doi.org/10.1172/JCI80631</a>.","apa":"Ebner, F., Sedlyarov, V., Tasciyan, S., Ivin, M., Kratochvill, F., Gratz, N., … Kovarik, P. (2017). The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection. <i>The Journal of Clinical Investigation</i>. American Society for Clinical Investigation. <a href=\"https://doi.org/10.1172/JCI80631\">https://doi.org/10.1172/JCI80631</a>","ama":"Ebner F, Sedlyarov V, Tasciyan S, et al. The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection. <i>The Journal of Clinical Investigation</i>. 2017;127(6):2051-2065. doi:<a href=\"https://doi.org/10.1172/JCI80631\">10.1172/JCI80631</a>","ista":"Ebner F, Sedlyarov V, Tasciyan S, Ivin M, Kratochvill F, Gratz N, Kenner L, Villunger A, Sixt MK, Kovarik P. 2017. The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection. The Journal of Clinical Investigation. 127(6), 2051–2065.","mla":"Ebner, Florian, et al. “The RNA-Binding Protein Tristetraprolin Schedules Apoptosis of Pathogen-Engaged Neutrophils during Bacterial Infection.” <i>The Journal of Clinical Investigation</i>, vol. 127, no. 6, American Society for Clinical Investigation, 2017, pp. 2051–65, doi:<a href=\"https://doi.org/10.1172/JCI80631\">10.1172/JCI80631</a>.","short":"F. Ebner, V. Sedlyarov, S. Tasciyan, M. Ivin, F. Kratochvill, N. Gratz, L. Kenner, A. Villunger, M.K. Sixt, P. Kovarik, The Journal of Clinical Investigation 127 (2017) 2051–2065."},"year":"2017","date_updated":"2024-03-25T23:30:12Z","external_id":{"pmid":["28504646"]}},{"month":"07","oa_version":"Published Version","publication":"Journal of Cell Science","has_accepted_license":"1","language":[{"iso":"eng"}],"oa":1,"publist_id":"7008","publication_identifier":{"issn":["00219533"]},"date_published":"2017-07-01T00:00:00Z","type":"journal_article","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_created":"2019-10-24T09:43:56Z","checksum":"42c81a0a4fc3128883b391c3af3f74bc","file_size":10847596,"date_updated":"2020-07-14T12:47:45Z","content_type":"application/pdf","file_name":"2017_CellScience_Vess.pdf","access_level":"open_access","relation":"main_file","file_id":"6966","creator":"dernst"}],"title":"A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity","intvolume":"       130","publication_status":"published","date_created":"2018-12-11T11:47:58Z","department":[{"_id":"MiSi"}],"author":[{"full_name":"Veß, Astrid","last_name":"Veß","first_name":"Astrid"},{"first_name":"Ulrich","last_name":"Blache","full_name":"Blache, Ulrich"},{"full_name":"Leitner, Laura","first_name":"Laura","last_name":"Leitner"},{"first_name":"Angela","last_name":"Kurz","full_name":"Kurz, Angela"},{"first_name":"Anja","last_name":"Ehrenpfordt","full_name":"Ehrenpfordt, Anja"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"},{"last_name":"Posern","first_name":"Guido","full_name":"Posern, Guido"}],"issue":"13","pmid":1,"_id":"694","scopus_import":1,"article_type":"original","publisher":"Company of Biologists","file_date_updated":"2020-07-14T12:47:45Z","page":"2172 - 2184","quality_controlled":"1","abstract":[{"text":"A change regarding the extent of adhesion - hereafter referred to as adhesion plasticity - between adhesive and less-adhesive states of mammalian cells is important for their behavior. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of human MDA-MB-468 breast carcinoma cells growing in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By using transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced at mRNA and protein levels in suspension cells. Furthermore, by transiently challenging breast cancer cells to grow under non-adherent conditions markedly reduces Tns3 protein expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental MDA-MB-468 cells results in defective adhesion, spreading and migration. Tns3-knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 protein expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a crucial focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.","lang":"eng"}],"doi":"10.1242/jcs.200899","day":"01","external_id":{"pmid":["28515231"]},"date_updated":"2021-01-12T08:09:41Z","year":"2017","citation":{"chicago":"Veß, Astrid, Ulrich Blache, Laura Leitner, Angela Kurz, Anja Ehrenpfordt, Michael K Sixt, and Guido Posern. “A Dual Phenotype of MDA MB 468 Cancer Cells Reveals Mutual Regulation of Tensin3 and Adhesion Plasticity.” <i>Journal of Cell Science</i>. Company of Biologists, 2017. <a href=\"https://doi.org/10.1242/jcs.200899\">https://doi.org/10.1242/jcs.200899</a>.","ieee":"A. Veß <i>et al.</i>, “A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity,” <i>Journal of Cell Science</i>, vol. 130, no. 13. Company of Biologists, pp. 2172–2184, 2017.","apa":"Veß, A., Blache, U., Leitner, L., Kurz, A., Ehrenpfordt, A., Sixt, M. K., &#38; Posern, G. (2017). A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity. <i>Journal of Cell Science</i>. Company of Biologists. <a href=\"https://doi.org/10.1242/jcs.200899\">https://doi.org/10.1242/jcs.200899</a>","ama":"Veß A, Blache U, Leitner L, et al. A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity. <i>Journal of Cell Science</i>. 2017;130(13):2172-2184. doi:<a href=\"https://doi.org/10.1242/jcs.200899\">10.1242/jcs.200899</a>","ista":"Veß A, Blache U, Leitner L, Kurz A, Ehrenpfordt A, Sixt MK, Posern G. 2017. A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity. Journal of Cell Science. 130(13), 2172–2184.","mla":"Veß, Astrid, et al. “A Dual Phenotype of MDA MB 468 Cancer Cells Reveals Mutual Regulation of Tensin3 and Adhesion Plasticity.” <i>Journal of Cell Science</i>, vol. 130, no. 13, Company of Biologists, 2017, pp. 2172–84, doi:<a href=\"https://doi.org/10.1242/jcs.200899\">10.1242/jcs.200899</a>.","short":"A. Veß, U. Blache, L. Leitner, A. Kurz, A. Ehrenpfordt, M.K. Sixt, G. Posern, Journal of Cell Science 130 (2017) 2172–2184."},"ddc":["570"],"volume":130},{"ec_funded":1,"quality_controlled":"1","page":"188 - 200","publisher":"Cell Press","issue":"1","author":[{"first_name":"Jan","last_name":"Mueller","full_name":"Mueller, Jan"},{"id":"4BFB7762-F248-11E8-B48F-1D18A9856A87","full_name":"Szep, Gregory","first_name":"Gregory","last_name":"Szep"},{"full_name":"Nemethova, Maria","last_name":"Nemethova","first_name":"Maria","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"full_name":"Lieber, Arnon","last_name":"Lieber","first_name":"Arnon"},{"last_name":"Winkler","first_name":"Christoph","full_name":"Winkler, Christoph"},{"last_name":"Kruse","first_name":"Karsten","full_name":"Kruse, Karsten"},{"full_name":"Small, John","first_name":"John","last_name":"Small"},{"full_name":"Schmeiser, Christian","first_name":"Christian","last_name":"Schmeiser"},{"full_name":"Keren, Kinneret","last_name":"Keren","first_name":"Kinneret"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"727","intvolume":"       171","title":"Load adaptation of lamellipodial actin networks","date_created":"2018-12-11T11:48:10Z","department":[{"_id":"MiSi"},{"_id":"Bio"}],"article_processing_charge":"No","publication_status":"published","volume":171,"external_id":{"isi":["000411331800020"]},"isi":1,"year":"2017","citation":{"ista":"Mueller J, Szep G, Nemethova M, de Vries I, Lieber A, Winkler C, Kruse K, Small J, Schmeiser C, Keren K, Hauschild R, Sixt MK. 2017. Load adaptation of lamellipodial actin networks. Cell. 171(1), 188–200.","mla":"Mueller, Jan, et al. “Load Adaptation of Lamellipodial Actin Networks.” <i>Cell</i>, vol. 171, no. 1, Cell Press, 2017, pp. 188–200, doi:<a href=\"https://doi.org/10.1016/j.cell.2017.07.051\">10.1016/j.cell.2017.07.051</a>.","short":"J. Mueller, G. Szep, M. Nemethova, I. de Vries, A. Lieber, C. Winkler, K. Kruse, J. Small, C. Schmeiser, K. Keren, R. Hauschild, M.K. Sixt, Cell 171 (2017) 188–200.","ieee":"J. Mueller <i>et al.</i>, “Load adaptation of lamellipodial actin networks,” <i>Cell</i>, vol. 171, no. 1. Cell Press, pp. 188–200, 2017.","chicago":"Mueller, Jan, Gregory Szep, Maria Nemethova, Ingrid de Vries, Arnon Lieber, Christoph Winkler, Karsten Kruse, et al. “Load Adaptation of Lamellipodial Actin Networks.” <i>Cell</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cell.2017.07.051\">https://doi.org/10.1016/j.cell.2017.07.051</a>.","apa":"Mueller, J., Szep, G., Nemethova, M., de Vries, I., Lieber, A., Winkler, C., … Sixt, M. K. (2017). Load adaptation of lamellipodial actin networks. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2017.07.051\">https://doi.org/10.1016/j.cell.2017.07.051</a>","ama":"Mueller J, Szep G, Nemethova M, et al. Load adaptation of lamellipodial actin networks. <i>Cell</i>. 2017;171(1):188-200. doi:<a href=\"https://doi.org/10.1016/j.cell.2017.07.051\">10.1016/j.cell.2017.07.051</a>"},"date_updated":"2023-09-28T11:33:49Z","abstract":[{"text":"Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.","lang":"eng"}],"day":"21","doi":"10.1016/j.cell.2017.07.051","language":[{"iso":"eng"}],"publication":"Cell","month":"09","project":[{"grant_number":"LS13-029","name":"Modeling of Polarization and Motility of Leukocytes in Three-Dimensional Environments","_id":"25AD6156-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556"}],"oa_version":"None","acknowledged_ssus":[{"_id":"ScienComp"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","type":"journal_article","date_published":"2017-09-21T00:00:00Z","publist_id":"6951","publication_identifier":{"issn":["00928674"]}},{"file":[{"file_size":236204020,"checksum":"3d6942d47d0737d064706b5728c4d8c8","date_created":"2018-12-12T13:02:47Z","file_name":"IST-2017-71-v1+1_Synapse_1.avi","content_type":"video/x-msvideo","date_updated":"2020-07-14T12:47:04Z","relation":"main_file","access_level":"open_access","creator":"system","file_id":"5612"},{"file_name":"IST-2017-71-v1+2_Synapse_2.avi","content_type":"video/x-msvideo","date_updated":"2020-07-14T12:47:04Z","file_size":226232496,"checksum":"4850006c047b0147a9e85b3c2f6f0af4","date_created":"2018-12-12T13:02:51Z","creator":"system","file_id":"5613","relation":"main_file","access_level":"open_access"}],"ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","day":"09","doi":"10.15479/AT:ISTA:71","oa":1,"abstract":[{"lang":"eng","text":"Immunological synapse DC-Tcells"}],"year":"2017","citation":{"ista":"Leithner AF. 2017. Immunological synapse DC-Tcells, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:71\">10.15479/AT:ISTA:71</a>.","short":"A.F. Leithner, (2017).","mla":"Leithner, Alexander F. <i>Immunological Synapse DC-Tcells</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:71\">10.15479/AT:ISTA:71</a>.","ieee":"A. F. Leithner, “Immunological synapse DC-Tcells.” Institute of Science and Technology Austria, 2017.","chicago":"Leithner, Alexander F. “Immunological Synapse DC-Tcells.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:71\">https://doi.org/10.15479/AT:ISTA:71</a>.","ama":"Leithner AF. Immunological synapse DC-Tcells. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:71\">10.15479/AT:ISTA:71</a>","apa":"Leithner, A. F. (2017). Immunological synapse DC-Tcells. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:71\">https://doi.org/10.15479/AT:ISTA:71</a>"},"date_updated":"2024-02-21T13:47:00Z","tmp":{"legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","short":"CC0 (1.0)","name":"Creative Commons Public Domain Dedication (CC0 1.0)","image":"/images/cc_0.png"},"type":"research_data","date_published":"2017-08-09T00:00:00Z","publisher":"Institute of Science and Technology Austria","keyword":["Immunological synapse"],"file_date_updated":"2020-07-14T12:47:04Z","department":[{"_id":"MiSi"}],"article_processing_charge":"No","date_created":"2018-12-12T12:31:34Z","oa_version":"Published Version","title":"Immunological synapse DC-Tcells","month":"08","has_accepted_license":"1","_id":"5567","datarep_id":"71","author":[{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X"}]},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2017-11-06T00:00:00Z","publication_identifier":{"issn":["2050084X"]},"publist_id":"7245","oa":1,"file":[{"date_updated":"2020-07-14T12:47:10Z","content_type":"application/pdf","file_name":"IST-2017-919-v1+1_elife-30867-figures-v1.pdf","date_created":"2018-12-12T10:10:40Z","checksum":"ba09c1451153d39e4f4b7cee013e314c","file_size":9666973,"file_id":"4829","creator":"system","access_level":"open_access","relation":"main_file"},{"date_created":"2018-12-12T10:10:41Z","checksum":"01eb51f1d6ad679947415a51c988e137","file_size":5951246,"date_updated":"2020-07-14T12:47:10Z","file_name":"IST-2017-919-v1+2_elife-30867-v1.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"4830","creator":"system"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","has_accepted_license":"1","publication":"eLife","oa_version":"Published Version","article_number":"e30867","month":"11","language":[{"iso":"eng"}],"citation":{"ista":"Spira F, Cuylen Haering S, Mehta S, Samwer M, Reversat A, Verma A, Oldenbourg R, Sixt MK, Gerlich D. 2017. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. eLife. 6, e30867.","mla":"Spira, Felix, et al. “Cytokinesis in Vertebrate Cells Initiates by Contraction of an Equatorial Actomyosin Network Composed of Randomly Oriented Filaments.” <i>ELife</i>, vol. 6, e30867, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.30867\">10.7554/eLife.30867</a>.","short":"F. Spira, S. Cuylen Haering, S. Mehta, M. Samwer, A. Reversat, A. Verma, R. Oldenbourg, M.K. Sixt, D. Gerlich, ELife 6 (2017).","chicago":"Spira, Felix, Sara Cuylen Haering, Shalin Mehta, Matthias Samwer, Anne Reversat, Amitabh Verma, Rudolf Oldenbourg, Michael K Sixt, and Daniel Gerlich. “Cytokinesis in Vertebrate Cells Initiates by Contraction of an Equatorial Actomyosin Network Composed of Randomly Oriented Filaments.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.30867\">https://doi.org/10.7554/eLife.30867</a>.","ieee":"F. Spira <i>et al.</i>, “Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ama":"Spira F, Cuylen Haering S, Mehta S, et al. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.30867\">10.7554/eLife.30867</a>","apa":"Spira, F., Cuylen Haering, S., Mehta, S., Samwer, M., Reversat, A., Verma, A., … Gerlich, D. (2017). Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.30867\">https://doi.org/10.7554/eLife.30867</a>"},"year":"2017","date_updated":"2023-02-23T12:30:29Z","day":"06","doi":"10.7554/eLife.30867","abstract":[{"lang":"eng","text":"The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings."}],"volume":6,"ddc":["570"],"scopus_import":1,"_id":"569","author":[{"full_name":"Spira, Felix","last_name":"Spira","first_name":"Felix"},{"full_name":"Cuylen Haering, Sara","last_name":"Cuylen Haering","first_name":"Sara"},{"full_name":"Mehta, Shalin","first_name":"Shalin","last_name":"Mehta"},{"first_name":"Matthias","last_name":"Samwer","full_name":"Samwer, Matthias"},{"id":"35B76592-F248-11E8-B48F-1D18A9856A87","last_name":"Reversat","first_name":"Anne","full_name":"Reversat, Anne","orcid":"0000-0003-0666-8928"},{"first_name":"Amitabh","last_name":"Verma","full_name":"Verma, Amitabh"},{"first_name":"Rudolf","last_name":"Oldenbourg","full_name":"Oldenbourg, Rudolf"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K"},{"last_name":"Gerlich","first_name":"Daniel","full_name":"Gerlich, Daniel"}],"department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:47:14Z","publication_status":"published","intvolume":"         6","pubrep_id":"919","title":"Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments","quality_controlled":"1","file_date_updated":"2020-07-14T12:47:10Z","publisher":"eLife Sciences Publications"},{"intvolume":"       171","title":"Migrating platelets are mechano scavengers that collect and bundle bacteria","department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:47:15Z","publication_status":"published","issue":"6","author":[{"full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","last_name":"Gärtner","first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Ahmad","first_name":"Zerkah","full_name":"Ahmad, Zerkah"},{"full_name":"Rosenberger, Gerhild","first_name":"Gerhild","last_name":"Rosenberger"},{"full_name":"Fan, Shuxia","first_name":"Shuxia","last_name":"Fan"},{"first_name":"Leo","last_name":"Nicolai","full_name":"Nicolai, Leo"},{"full_name":"Busch, Benjamin","first_name":"Benjamin","last_name":"Busch"},{"first_name":"Gökce","last_name":"Yavuz","full_name":"Yavuz, Gökce"},{"last_name":"Luckner","first_name":"Manja","full_name":"Luckner, Manja"},{"last_name":"Ishikawa Ankerhold","first_name":"Hellen","full_name":"Ishikawa Ankerhold, Hellen"},{"first_name":"Roman","last_name":"Hennel","full_name":"Hennel, Roman"},{"first_name":"Alexandre","last_name":"Benechet","full_name":"Benechet, Alexandre"},{"first_name":"Michael","last_name":"Lorenz","full_name":"Lorenz, Michael"},{"first_name":"Sue","last_name":"Chandraratne","full_name":"Chandraratne, Sue"},{"first_name":"Irene","last_name":"Schubert","full_name":"Schubert, Irene"},{"last_name":"Helmer","first_name":"Sebastian","full_name":"Helmer, Sebastian"},{"first_name":"Bianca","last_name":"Striednig","full_name":"Striednig, Bianca"},{"full_name":"Stark, Konstantin","first_name":"Konstantin","last_name":"Stark"},{"full_name":"Janko, Marek","first_name":"Marek","last_name":"Janko"},{"full_name":"Böttcher, Ralph","last_name":"Böttcher","first_name":"Ralph"},{"full_name":"Verschoor, Admar","first_name":"Admar","last_name":"Verschoor"},{"full_name":"Leon, Catherine","last_name":"Leon","first_name":"Catherine"},{"last_name":"Gachet","first_name":"Christian","full_name":"Gachet, Christian"},{"full_name":"Gudermann, Thomas","first_name":"Thomas","last_name":"Gudermann"},{"full_name":"Mederos Y Schnitzler, Michael","last_name":"Mederos Y Schnitzler","first_name":"Michael"},{"full_name":"Pincus, Zachary","first_name":"Zachary","last_name":"Pincus"},{"full_name":"Iannacone, Matteo","last_name":"Iannacone","first_name":"Matteo"},{"first_name":"Rainer","last_name":"Haas","full_name":"Haas, Rainer"},{"full_name":"Wanner, Gerhard","first_name":"Gerhard","last_name":"Wanner"},{"first_name":"Kirsten","last_name":"Lauber","full_name":"Lauber, Kirsten"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Massberg, Steffen","last_name":"Massberg","first_name":"Steffen"}],"scopus_import":1,"_id":"571","publisher":"Cell Press","quality_controlled":"1","ec_funded":1,"page":"1368 - 1382","abstract":[{"text":"Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. In addition to their role in thrombosis and hemostasis, platelets can also migrate to sites of infection to help trap bacteria and clear the vascular surface.","lang":"eng"}],"day":"30","doi":"10.1016/j.cell.2017.11.001","citation":{"ista":"Gärtner FR, Ahmad Z, Rosenberger G, Fan S, Nicolai L, Busch B, Yavuz G, Luckner M, Ishikawa Ankerhold H, Hennel R, Benechet A, Lorenz M, Chandraratne S, Schubert I, Helmer S, Striednig B, Stark K, Janko M, Böttcher R, Verschoor A, Leon C, Gachet C, Gudermann T, Mederos Y Schnitzler M, Pincus Z, Iannacone M, Haas R, Wanner G, Lauber K, Sixt MK, Massberg S. 2017. Migrating platelets are mechano scavengers that collect and bundle bacteria. Cell Press. 171(6), 1368–1382.","mla":"Gärtner, Florian R., et al. “Migrating Platelets Are Mechano Scavengers That Collect and Bundle Bacteria.” <i>Cell Press</i>, vol. 171, no. 6, Cell Press, 2017, pp. 1368–82, doi:<a href=\"https://doi.org/10.1016/j.cell.2017.11.001\">10.1016/j.cell.2017.11.001</a>.","short":"F.R. Gärtner, Z. Ahmad, G. Rosenberger, S. Fan, L. Nicolai, B. Busch, G. Yavuz, M. Luckner, H. Ishikawa Ankerhold, R. Hennel, A. Benechet, M. Lorenz, S. Chandraratne, I. Schubert, S. Helmer, B. Striednig, K. Stark, M. Janko, R. Böttcher, A. Verschoor, C. Leon, C. Gachet, T. Gudermann, M. Mederos Y Schnitzler, Z. Pincus, M. Iannacone, R. Haas, G. Wanner, K. Lauber, M.K. Sixt, S. Massberg, Cell Press 171 (2017) 1368–1382.","chicago":"Gärtner, Florian R, Zerkah Ahmad, Gerhild Rosenberger, Shuxia Fan, Leo Nicolai, Benjamin Busch, Gökce Yavuz, et al. “Migrating Platelets Are Mechano Scavengers That Collect and Bundle Bacteria.” <i>Cell Press</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cell.2017.11.001\">https://doi.org/10.1016/j.cell.2017.11.001</a>.","ieee":"F. R. Gärtner <i>et al.</i>, “Migrating platelets are mechano scavengers that collect and bundle bacteria,” <i>Cell Press</i>, vol. 171, no. 6. Cell Press, pp. 1368–1382, 2017.","ama":"Gärtner FR, Ahmad Z, Rosenberger G, et al. Migrating platelets are mechano scavengers that collect and bundle bacteria. <i>Cell Press</i>. 2017;171(6):1368-1382. doi:<a href=\"https://doi.org/10.1016/j.cell.2017.11.001\">10.1016/j.cell.2017.11.001</a>","apa":"Gärtner, F. R., Ahmad, Z., Rosenberger, G., Fan, S., Nicolai, L., Busch, B., … Massberg, S. (2017). Migrating platelets are mechano scavengers that collect and bundle bacteria. <i>Cell Press</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2017.11.001\">https://doi.org/10.1016/j.cell.2017.11.001</a>"},"year":"2017","date_updated":"2021-01-12T08:03:15Z","volume":171,"month":"11","project":[{"grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"oa_version":"None","publication":"Cell Press","language":[{"iso":"eng"}],"publist_id":"7243","publication_identifier":{"issn":["00928674"]},"type":"journal_article","date_published":"2017-11-30T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public"},{"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"Nature Communications","oa_version":"Published Version","article_number":"14832","month":"03","file":[{"relation":"main_file","access_level":"open_access","creator":"system","file_id":"5072","file_size":9523746,"checksum":"dae30190291c3630e8102d8714a8d23e","date_created":"2018-12-12T10:14:21Z","file_name":"IST-2017-902-v1+1_Kage_et_al-2017-Nature_Communications.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:34Z"}],"status":"public","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2017-03-22T00:00:00Z","publication_identifier":{"issn":["20411723"]},"oa":1,"publist_id":"7075","quality_controlled":"1","file_date_updated":"2020-07-14T12:47:34Z","publisher":"Nature Publishing Group","scopus_import":1,"_id":"659","author":[{"first_name":"Frieda","last_name":"Kage","full_name":"Kage, Frieda"},{"first_name":"Moritz","last_name":"Winterhoff","full_name":"Winterhoff, Moritz"},{"full_name":"Dimchev, Vanessa","first_name":"Vanessa","last_name":"Dimchev"},{"full_name":"Müller, Jan","last_name":"Müller","first_name":"Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"first_name":"Tobias","last_name":"Thalheim","full_name":"Thalheim, Tobias"},{"full_name":"Freise, Anika","last_name":"Freise","first_name":"Anika"},{"last_name":"Brühmann","first_name":"Stefan","full_name":"Brühmann, Stefan"},{"full_name":"Kollasser, Jana","last_name":"Kollasser","first_name":"Jana"},{"last_name":"Block","first_name":"Jennifer","full_name":"Block, Jennifer"},{"full_name":"Dimchev, Georgi A","first_name":"Georgi A","last_name":"Dimchev"},{"first_name":"Matthias","last_name":"Geyer","full_name":"Geyer, Matthias"},{"first_name":"Hams","last_name":"Schnittler","full_name":"Schnittler, Hams"},{"first_name":"Cord","last_name":"Brakebusch","full_name":"Brakebusch, Cord"},{"full_name":"Stradal, Theresia","first_name":"Theresia","last_name":"Stradal"},{"last_name":"Carlier","first_name":"Marie","full_name":"Carlier, Marie"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"},{"last_name":"Käs","first_name":"Josef","full_name":"Käs, Josef"},{"full_name":"Faix, Jan","first_name":"Jan","last_name":"Faix"},{"last_name":"Rottner","first_name":"Klemens","full_name":"Rottner, Klemens"}],"date_created":"2018-12-11T11:47:46Z","article_processing_charge":"No","department":[{"_id":"MiSi"}],"publication_status":"published","intvolume":"         8","pubrep_id":"902","title":"FMNL formins boost lamellipodial force generation","volume":8,"ddc":["570"],"year":"2017","citation":{"ista":"Kage F, Winterhoff M, Dimchev V, Müller J, Thalheim T, Freise A, Brühmann S, Kollasser J, Block J, Dimchev GA, Geyer M, Schnittler H, Brakebusch C, Stradal T, Carlier M, Sixt MK, Käs J, Faix J, Rottner K. 2017. FMNL formins boost lamellipodial force generation. Nature Communications. 8, 14832.","mla":"Kage, Frieda, et al. “FMNL Formins Boost Lamellipodial Force Generation.” <i>Nature Communications</i>, vol. 8, 14832, Nature Publishing Group, 2017, doi:<a href=\"https://doi.org/10.1038/ncomms14832\">10.1038/ncomms14832</a>.","short":"F. Kage, M. Winterhoff, V. Dimchev, J. Müller, T. Thalheim, A. Freise, S. Brühmann, J. Kollasser, J. Block, G.A. Dimchev, M. Geyer, H. Schnittler, C. Brakebusch, T. Stradal, M. Carlier, M.K. Sixt, J. Käs, J. Faix, K. Rottner, Nature Communications 8 (2017).","ieee":"F. Kage <i>et al.</i>, “FMNL formins boost lamellipodial force generation,” <i>Nature Communications</i>, vol. 8. Nature Publishing Group, 2017.","chicago":"Kage, Frieda, Moritz Winterhoff, Vanessa Dimchev, Jan Müller, Tobias Thalheim, Anika Freise, Stefan Brühmann, et al. “FMNL Formins Boost Lamellipodial Force Generation.” <i>Nature Communications</i>. Nature Publishing Group, 2017. <a href=\"https://doi.org/10.1038/ncomms14832\">https://doi.org/10.1038/ncomms14832</a>.","ama":"Kage F, Winterhoff M, Dimchev V, et al. FMNL formins boost lamellipodial force generation. <i>Nature Communications</i>. 2017;8. doi:<a href=\"https://doi.org/10.1038/ncomms14832\">10.1038/ncomms14832</a>","apa":"Kage, F., Winterhoff, M., Dimchev, V., Müller, J., Thalheim, T., Freise, A., … Rottner, K. (2017). FMNL formins boost lamellipodial force generation. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncomms14832\">https://doi.org/10.1038/ncomms14832</a>"},"date_updated":"2021-01-12T08:08:06Z","day":"22","doi":"10.1038/ncomms14832","abstract":[{"text":"Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.","lang":"eng"}]},{"abstract":[{"lang":"eng","text":"Directed cell migration is a hallmark feature, present in almost all multi-cellular\r\norganisms. Despite its importance, basic questions regarding force transduction\r\nor directional sensing are still heavily investigated. Directed migration of cells\r\nguided by immobilized guidance cues - haptotaxis - occurs in key-processes,\r\nsuch as embryonic development and immunity (Middleton et al., 1997; Nguyen\r\net al., 2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues\r\ncomprise adhesive ligands, such as collagen and fibronectin (Barczyk et al.,\r\n2009), or chemokines - the main guidance cues for migratory leukocytes\r\n(Middleton et al., 1997; Weber et al., 2013). While adhesive ligands serve as\r\nattachment sites guiding cell migration (Carter, 1965), chemokines instruct\r\nhaptotactic migration by inducing adhesion to adhesive ligands and directional\r\nguidance (Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis\r\nof the cellular response to immobilized guidance cues requires in vitro assays\r\nthat foster cell migration, offer accurate control of the immobilized cues on a\r\nsubcellular scale and in the ideal case closely reproduce in vivo conditions. The\r\nexploration of haptotactic cell migration through design and employment of such\r\nassays represents the main focus of this work.\r\nDendritic cells (DCs) are leukocytes, which after encountering danger\r\nsignals such as pathogens in peripheral organs instruct naïve T-cells and\r\nconsequently the adaptive immune response in the lymph node (Mellman and\r\nSteinman, 2001). To reach the lymph node from the periphery, DCs follow\r\nhaptotactic gradients of the chemokine CCL21 towards lymphatic vessels\r\n(Weber et al., 2013). Questions about how DCs interpret haptotactic CCL21\r\ngradients have not yet been addressed. The main reason for this is the lack of\r\nan assay that offers diverse haptotactic environments, hence allowing the study\r\nof DC migration as a response to different signals of immobilized guidance cue.\r\nIn this work, we developed an in vitro assay that enables us to\r\nquantitatively assess DC haptotaxis, by combining precisely controllable\r\nchemokine photo-patterning with physically confining migration conditions. With this tool at hand, we studied the influence of CCL21 gradient properties and\r\nconcentration on DC haptotaxis. We found that haptotactic gradient sensing\r\ndepends on the absolute CCL21 concentration in combination with the local\r\nsteepness of the gradient. Our analysis suggests that the directionality of\r\nmigrating DCs is governed by the signal-to-noise ratio of CCL21 binding to its\r\nreceptor CCR7. Moreover, the haptotactic CCL21 gradient formed in vivo\r\nprovides an optimal shape for DCs to recognize haptotactic guidance cue.\r\nBy reconstitution of the CCL21 gradient in vitro we were also able to\r\nstudy the influence of CCR7 signal termination on DC haptotaxis. To this end,\r\nwe used DCs lacking the G-protein coupled receptor kinase GRK6, which is\r\nresponsible for CCL21 induced CCR7 receptor phosphorylation and\r\ndesensitization (Zidar et al., 2009). We found that CCR7 desensitization by\r\nGRK6 is crucial for maintenance of haptotactic CCL21 gradient sensing in vitro\r\nand confirm those observations in vivo.\r\nIn the context of the organism, immobilized haptotactic guidance cues\r\noften coincide and compete with soluble chemotactic guidance cues. During\r\nwound healing, fibroblasts are exposed and influenced by adhesive cues and\r\nsoluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,\r\nmigrating DCs are exposed to both, soluble chemokines (CCL19 and truncated\r\nCCL21) inducing chemotactic behavior as well as the immobilized CCL21. To\r\nquantitatively assess these complex coinciding immobilized and soluble\r\nguidance cues, we implemented our chemokine photo-patterning technique in a\r\nmicrofluidic system allowing for chemotactic gradient generation. To validate\r\nthe assay, we observed DC migration in competing CCL19/CCL21\r\nenvironments.\r\nAdhesiveness guided haptotaxis has been studied intensively over the\r\nlast century. However, quantitative studies leading to conceptual models are\r\nlargely missing, again due to the lack of a precisely controllable in vitro assay. A\r\nrequirement for such an in vitro assay is that it must prevent any uncontrolled\r\ncell adhesion. This can be accomplished by stable passivation of the surface. In\r\naddition, controlled adhesion must be sustainable, quantifiable and dose\r\ndependent in order to create homogenous gradients. Therefore, we developed a novel covalent photo-patterning technique satisfying all these needs. In\r\ncombination with a sustainable poly-vinyl alcohol (PVA) surface coating we\r\nwere able to generate gradients of adhesive cue to direct cell migration. This\r\napproach allowed us to characterize the haptotactic migratory behavior of\r\nzebrafish keratocytes in vitro. Furthermore, defined patterns of adhesive cue\r\nallowed us to control for cell shape and growth on a subcellular scale."}],"degree_awarded":"PhD","day":"01","date_updated":"2023-09-07T11:54:33Z","year":"2016","citation":{"ista":"Schwarz J. 2016. Quantitative analysis of haptotactic cell migration. Institute of Science and Technology Austria.","mla":"Schwarz, Jan. <i>Quantitative Analysis of Haptotactic Cell Migration</i>. Institute of Science and Technology Austria, 2016.","short":"J. Schwarz, Quantitative Analysis of Haptotactic Cell Migration, Institute of Science and Technology Austria, 2016.","chicago":"Schwarz, Jan. “Quantitative Analysis of Haptotactic Cell Migration.” Institute of Science and Technology Austria, 2016.","ieee":"J. Schwarz, “Quantitative analysis of haptotactic cell migration,” Institute of Science and Technology Austria, 2016.","apa":"Schwarz, J. (2016). <i>Quantitative analysis of haptotactic cell migration</i>. Institute of Science and Technology Austria.","ama":"Schwarz J. Quantitative analysis of haptotactic cell migration. 2016."},"ddc":["570"],"acknowledgement":"First, I would like to thank Michael Sixt for being a great supervisor, mentor and\r\nscientist. I highly appreciate his guidance and continued support. Furthermore, I\r\nam very grateful that he gave me the exceptional opportunity to pursue many\r\nideas of which some managed to be included in this thesis.\r\nI owe sincere thanks to the members of my PhD thesis committee, Daria\r\nSiekhaus, Daniel Legler and Harald Janovjak. Especially I would like to thank\r\nDaria for her advice and encouragement during our regular progress meetings.\r\nI also want to thank the team and fellows of the Boehringer Ingelheim Fond\r\n(BIF) PhD Fellowship for amazing and inspiring meetings and the BIF for\r\nfinancial support.\r\nImportant factors for the success of this thesis were the warm, creative\r\nand helpful atmosphere as well as the team spirit of the whole Sixt Lab.\r\nTherefore I would like to thank my current and former colleagues Frank Assen,\r\nMarkus Brown, Ingrid de Vries, Michelle Duggan, Alexander Eichner, Miroslav\r\nHons, Eva Kiermaier, Aglaja Kopf, Alexander Leithner, Christine Moussion, Jan\r\nMüller, Maria Nemethova, Jörg Renkawitz, Anne Reversat, Kari Vaahtomeri,\r\nMichele Weber and Stefan Wieser. We had an amazing time with many\r\nlegendary evenings and events. Along these lines I want to thank the in vitro\r\ncrew of the lab, Jörg, Anne and Alex, for lots of ideas and productive\r\ndiscussions. I am sure, some day we will reveal the secret of the ‘splodge’.\r\nI want to thank the members of the Heisenberg Lab for a great time and\r\nthrilling kicker matches. In this regard I especially want to thank Maurizio\r\n‘Gnocci’ Monti, Gabriel Krens, Alex Eichner, Martin Behrndt, Vanessa Barone,Philipp Schmalhorst, Michael Smutny, Daniel Capek, Anne Reversat, Eva\r\nKiermaier, Frank Assen and Jan Müller for wonderful after-lunch matches.\r\nI would not have been able to analyze the thousands of cell trajectories\r\nand probably hundreds of thousands of mouse clicks without the productive\r\ncollaboration with Veronika Bierbaum and Tobias Bollenbach. Thanks Vroni for\r\ncountless meetings, discussions and graphs and of course for proofreading and\r\nadvice for this thesis. For proofreading I also want to thank Evi, Jörg, Jack and\r\nAnne.\r\nI would like to acknowledge Matthias Mehling for a very productive\r\ncollaboration and for introducing me into the wild world of microfluidics. Jack\r\nMerrin, for countless wafers, PDMS coated coverslips and help with anything\r\nmicro-fabrication related. And Maria Nemethova for establishing the ‘click’\r\npatterning approach with me. Without her it still would be just one of the ideas…\r\nMany thanks to Ekaterina Papusheva, Robert Hauschild, Doreen Milius\r\nand Nasser Darwish from the Bioimaging Facility as well as the Preclinical and\r\nthe Life Science facilities of IST Austria for excellent technical support. At this\r\npoint I especially want to thank Robert for countless image analyses and\r\ntechnical ideas. Always interested and creative he played an essential role in all\r\nof my projects.\r\nAdditionally I want to thank Ingrid and Gabby for welcoming me warmly\r\nwhen I first started at IST, for scientific and especially mental support in all\r\nthose years, countless coffee sessions and Heurigen evenings. #BioimagingFacility #LifeScienceFacility #PreClinicalFacility","alternative_title":["ISTA Thesis"],"title":"Quantitative analysis of haptotactic cell migration","publication_status":"published","department":[{"_id":"MiSi"}],"article_processing_charge":"No","date_created":"2018-12-11T11:50:18Z","author":[{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz"}],"_id":"1129","publisher":"Institute of Science and Technology Austria","file_date_updated":"2021-02-22T11:43:14Z","page":"178","supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"oa":1,"publist_id":"6231","publication_identifier":{"issn":["2663-337X"]},"date_published":"2016-07-01T00:00:00Z","type":"dissertation","status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"relation":"main_file","access_level":"closed","file_id":"6813","creator":"dernst","date_created":"2019-08-13T10:55:35Z","checksum":"e3cd6b28f9c5cccb8891855565a2dade","file_size":32044069,"date_updated":"2019-08-13T10:55:35Z","content_type":"application/pdf","file_name":"Thesis_JSchwarz_final.pdf"},{"success":1,"access_level":"open_access","relation":"main_file","creator":"dernst","file_id":"9181","checksum":"c3dbe219acf87eed2f46d21d5cca00de","file_size":8396717,"date_created":"2021-02-22T11:43:14Z","content_type":"application/pdf","file_name":"2016_Thesis_JSchwarz.pdf","date_updated":"2021-02-22T11:43:14Z"}],"month":"07","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"oa_version":"Published Version","has_accepted_license":"1","language":[{"iso":"eng"}]},{"publist_id":"6221","oa":1,"date_published":"2016-12-01T00:00:00Z","type":"journal_article","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400263"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","oa_version":"Submitted Version","month":"12","publication":"Nature Immunology","language":[{"iso":"eng"}],"doi":"10.1038/ni.3575","day":"01","abstract":[{"lang":"eng","text":"RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1. RASGRP1 deficiency also resulted in defective proliferation, activation and motility of T cells and B cells. RASGRP1-deficient natural killer (NK) cells exhibited impaired cytotoxicity with defective granule convergence and actin accumulation. Interaction proteomics identified the dynein light chain DYNLL1 as interacting with RASGRP1, which links RASGRP1 to cytoskeletal dynamics. RASGRP1-deficient cells showed decreased activation of the GTPase RhoA. Treatment with lenalidomide increased RhoA activity and reversed the migration and activation defects of RASGRP1-deficient lymphocytes."}],"date_updated":"2021-01-12T06:48:33Z","citation":{"short":"E. Salzer, D. Çaǧdaş, M. Hons, E. Mace, W. Garncarz, O. Petronczki, R. Platzer, L. Pfajfer, I. Bilic, S. Ban, K. Willmann, M. Mukherjee, V. Supper, H. Hsu, P. Banerjee, P. Sinha, F. Mcclanahan, G. Zlabinger, W. Pickl, J. Gribben, H. Stockinger, K. Bennett, J. Huppa, L. Dupré, Ö. Sanal, U. Jäger, M.K. Sixt, I. Tezcan, J. Orange, K. Boztug, Nature Immunology 17 (2016) 1352–1360.","mla":"Salzer, Elisabeth, et al. “RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics.” <i>Nature Immunology</i>, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1352–60, doi:<a href=\"https://doi.org/10.1038/ni.3575\">10.1038/ni.3575</a>.","ista":"Salzer E, Çaǧdaş D, Hons M, Mace E, Garncarz W, Petronczki O, Platzer R, Pfajfer L, Bilic I, Ban S, Willmann K, Mukherjee M, Supper V, Hsu H, Banerjee P, Sinha P, Mcclanahan F, Zlabinger G, Pickl W, Gribben J, Stockinger H, Bennett K, Huppa J, Dupré L, Sanal Ö, Jäger U, Sixt MK, Tezcan I, Orange J, Boztug K. 2016. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. 17(12), 1352–1360.","apa":"Salzer, E., Çaǧdaş, D., Hons, M., Mace, E., Garncarz, W., Petronczki, O., … Boztug, K. (2016). RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. <i>Nature Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ni.3575\">https://doi.org/10.1038/ni.3575</a>","ama":"Salzer E, Çaǧdaş D, Hons M, et al. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. <i>Nature Immunology</i>. 2016;17(12):1352-1360. doi:<a href=\"https://doi.org/10.1038/ni.3575\">10.1038/ni.3575</a>","chicago":"Salzer, Elisabeth, Deniz Çaǧdaş, Miroslav Hons, Emily Mace, Wojciech Garncarz, Oezlem Petronczki, René Platzer, et al. “RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics.” <i>Nature Immunology</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ni.3575\">https://doi.org/10.1038/ni.3575</a>.","ieee":"E. Salzer <i>et al.</i>, “RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics,” <i>Nature Immunology</i>, vol. 17, no. 12. Nature Publishing Group, pp. 1352–1360, 2016."},"year":"2016","external_id":{"pmid":["27776107"]},"volume":17,"publication_status":"published","department":[{"_id":"MiSi"}],"article_processing_charge":"No","date_created":"2018-12-11T11:50:21Z","title":"RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics","intvolume":"        17","pmid":1,"_id":"1137","scopus_import":1,"author":[{"last_name":"Salzer","first_name":"Elisabeth","full_name":"Salzer, Elisabeth"},{"full_name":"Çaǧdaş, Deniz","first_name":"Deniz","last_name":"Çaǧdaş"},{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslav","last_name":"Hons","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav"},{"last_name":"Mace","first_name":"Emily","full_name":"Mace, Emily"},{"full_name":"Garncarz, Wojciech","first_name":"Wojciech","last_name":"Garncarz"},{"first_name":"Oezlem","last_name":"Petronczki","full_name":"Petronczki, Oezlem"},{"last_name":"Platzer","first_name":"René","full_name":"Platzer, René"},{"last_name":"Pfajfer","first_name":"Laurène","full_name":"Pfajfer, Laurène"},{"full_name":"Bilic, Ivan","last_name":"Bilic","first_name":"Ivan"},{"first_name":"Sol","last_name":"Ban","full_name":"Ban, Sol"},{"last_name":"Willmann","first_name":"Katharina","full_name":"Willmann, Katharina"},{"first_name":"Malini","last_name":"Mukherjee","full_name":"Mukherjee, Malini"},{"full_name":"Supper, Verena","first_name":"Verena","last_name":"Supper"},{"full_name":"Hsu, Hsiangting","last_name":"Hsu","first_name":"Hsiangting"},{"last_name":"Banerjee","first_name":"Pinaki","full_name":"Banerjee, Pinaki"},{"full_name":"Sinha, Papiya","last_name":"Sinha","first_name":"Papiya"},{"last_name":"Mcclanahan","first_name":"Fabienne","full_name":"Mcclanahan, Fabienne"},{"full_name":"Zlabinger, Gerhard","first_name":"Gerhard","last_name":"Zlabinger"},{"full_name":"Pickl, Winfried","last_name":"Pickl","first_name":"Winfried"},{"last_name":"Gribben","first_name":"John","full_name":"Gribben, John"},{"full_name":"Stockinger, Hannes","first_name":"Hannes","last_name":"Stockinger"},{"full_name":"Bennett, Keiryn","last_name":"Bennett","first_name":"Keiryn"},{"first_name":"Johannes","last_name":"Huppa","full_name":"Huppa, Johannes"},{"full_name":"Dupré, Loï̈C","last_name":"Dupré","first_name":"Loï̈C"},{"last_name":"Sanal","first_name":"Özden","full_name":"Sanal, Özden"},{"full_name":"Jäger, Ulrich","first_name":"Ulrich","last_name":"Jäger"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tezcan, Ilhan","first_name":"Ilhan","last_name":"Tezcan"},{"first_name":"Jordan","last_name":"Orange","full_name":"Orange, Jordan"},{"full_name":"Boztug, Kaan","last_name":"Boztug","first_name":"Kaan"}],"issue":"12","publisher":"Nature Publishing Group","article_type":"original","page":"1352 - 1360","quality_controlled":"1"}]