[{"date_created":"2023-01-16T09:16:10Z","department":[{"_id":"XiFe"}],"language":[{"iso":"eng"}],"publisher":"Public Library of Science (PLoS)","scopus_import":"1","date_published":"2020-06-29T00:00:00Z","article_type":"original","month":"06","issue":"6","publication":"PLOS Genetics","status":"public","intvolume":"        16","type":"journal_article","day":"29","article_number":"e1008894","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351236/","open_access":"1"}],"title":"AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization","external_id":{"pmid":["32598340"]},"doi":"10.1371/journal.pgen.1008894","year":"2020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"The authors wish to thank Cécile Raynaud, Eric Jenczewski, Rajeev Kumar, Raphaël Mercier and Jean Molinier for critical reading of the manuscript.","quality_controlled":"1","oa_version":"Published Version","_id":"12189","pmid":1,"extern":"1","publication_identifier":{"issn":["1553-7404"]},"volume":16,"date_updated":"2023-05-08T10:54:39Z","oa":1,"article_processing_charge":"No","author":[{"first_name":"Nicolas","full_name":"Christophorou, Nicolas","last_name":"Christophorou"},{"first_name":"Wenjing","full_name":"She, Wenjing","last_name":"She"},{"first_name":"Jincheng","last_name":"Long","full_name":"Long, Jincheng"},{"first_name":"Aurélie","last_name":"Hurel","full_name":"Hurel, Aurélie"},{"last_name":"Beaubiat","full_name":"Beaubiat, Sébastien","first_name":"Sébastien"},{"full_name":"Idir, Yassir","last_name":"Idir","first_name":"Yassir"},{"full_name":"Tagliaro-Jahns, Marina","last_name":"Tagliaro-Jahns","first_name":"Marina"},{"first_name":"Aurélie","last_name":"Chambon","full_name":"Chambon, Aurélie"},{"last_name":"Solier","full_name":"Solier, Victor","first_name":"Victor"},{"last_name":"Vezon","full_name":"Vezon, Daniel","first_name":"Daniel"},{"last_name":"Grelon","full_name":"Grelon, Mathilde","first_name":"Mathilde"},{"id":"e0164712-22ee-11ed-b12a-d80fcdf35958","first_name":"Xiaoqi","orcid":"0000-0002-4008-1234","full_name":"Feng, Xiaoqi","last_name":"Feng"},{"first_name":"Nicolas","full_name":"Bouché, Nicolas","last_name":"Bouché"},{"full_name":"Mézard, Christine","last_name":"Mézard","first_name":"Christine"}],"keyword":["Cancer Research","Genetics (clinical)","Genetics","Molecular Biology","Ecology","Evolution","Behavior and Systematics"],"abstract":[{"text":"Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that meiotic COs are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation protein modification pathway in Arabidopsis thaliana. Here, we report that in axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the formation of the telomere bouquet is not affected. COs are also redistributed towards subtelomeric chromosomal ends where they frequently form clusters, in contrast to large central regions depleted in recombination. The CO suppressed regions correlate with DNA hypermethylation of transposable elements (TEs) in the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we found axr1-/- affects DNA methylation in a plant, causing hypermethylation in all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic cells but does not restore regular chromosome segregation during meiosis. Collectively, our findings reveal that the neddylation pathway not only regulates hormonal perception and CO distribution but is also, directly or indirectly, a major limiting pathway of TE DNA methylation in somatic cells.","lang":"eng"}],"publication_status":"published","citation":{"apa":"Christophorou, N., She, W., Long, J., Hurel, A., Beaubiat, S., Idir, Y., … Mézard, C. (2020). AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization. <i>PLOS Genetics</i>. Public Library of Science (PLoS). <a href=\"https://doi.org/10.1371/journal.pgen.1008894\">https://doi.org/10.1371/journal.pgen.1008894</a>","ieee":"N. Christophorou <i>et al.</i>, “AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization,” <i>PLOS Genetics</i>, vol. 16, no. 6. Public Library of Science (PLoS), 2020.","chicago":"Christophorou, Nicolas, Wenjing She, Jincheng Long, Aurélie Hurel, Sébastien Beaubiat, Yassir Idir, Marina Tagliaro-Jahns, et al. “AXR1 Affects DNA Methylation Independently of Its Role in Regulating Meiotic Crossover Localization.” <i>PLOS Genetics</i>. Public Library of Science (PLoS), 2020. <a href=\"https://doi.org/10.1371/journal.pgen.1008894\">https://doi.org/10.1371/journal.pgen.1008894</a>.","ama":"Christophorou N, She W, Long J, et al. AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization. <i>PLOS Genetics</i>. 2020;16(6). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1008894\">10.1371/journal.pgen.1008894</a>","mla":"Christophorou, Nicolas, et al. “AXR1 Affects DNA Methylation Independently of Its Role in Regulating Meiotic Crossover Localization.” <i>PLOS Genetics</i>, vol. 16, no. 6, e1008894, Public Library of Science (PLoS), 2020, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1008894\">10.1371/journal.pgen.1008894</a>.","ista":"Christophorou N, She W, Long J, Hurel A, Beaubiat S, Idir Y, Tagliaro-Jahns M, Chambon A, Solier V, Vezon D, Grelon M, Feng X, Bouché N, Mézard C. 2020. AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization. PLOS Genetics. 16(6), e1008894.","short":"N. Christophorou, W. She, J. Long, A. Hurel, S. Beaubiat, Y. Idir, M. Tagliaro-Jahns, A. Chambon, V. Solier, D. Vezon, M. Grelon, X. Feng, N. Bouché, C. Mézard, PLOS Genetics 16 (2020)."}},{"publication_identifier":{"issn":["1553-7404"]},"pmid":1,"_id":"7399","quality_controlled":"1","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","date_updated":"2023-10-17T12:30:27Z","volume":15,"oa":1,"abstract":[{"text":"Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, and many are thought to be involved in the regulation of gene expression. However, the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable. Imprinted lncRNAs target and recruit epigenetic silencing factors to a cluster of imprinted genes on the same chromosome, making them one of the best characterized lncRNAs for silencing distant genes in cis. In this study we examined silencing of the distant imprinted gene Slc22a3 by the lncRNA Airn in the Igf2r imprinted cluster in mouse. Previously we proposed that imprinted lncRNAs may silence distant imprinted genes by disrupting promoter-enhancer interactions by being transcribed through the enhancer, which we called the enhancer interference hypothesis. Here we tested this hypothesis by first using allele-specific chromosome conformation capture (3C) to detect interactions between the Slc22a3 promoter and the locus of the Airn lncRNA that silences it on the paternal chromosome. In agreement with the model, we found interactions enriched on the maternal allele across the entire Airn gene consistent with multiple enhancer-promoter interactions. Therefore, to test the enhancer interference hypothesis we devised an approach to delete the entire Airn gene. However, the deletion showed that there are no essential enhancers for Slc22a2, Pde10a and Slc22a3 within the Airn gene, strongly indicating that the Airn RNA rather than its transcription is responsible for silencing distant imprinted genes. Furthermore, we found that silent imprinted genes were covered with large blocks of H3K27me3 on the repressed paternal allele. Therefore we propose an alternative hypothesis whereby the chromosome interactions may initially guide the lncRNA to target imprinted promoters and recruit repressive chromatin, and that these interactions are lost once silencing is established.","lang":"eng"}],"author":[{"first_name":"Daniel","last_name":"Andergassen","full_name":"Andergassen, Daniel"},{"full_name":"Muckenhuber, Markus","last_name":"Muckenhuber","first_name":"Markus"},{"last_name":"Bammer","full_name":"Bammer, Philipp C.","first_name":"Philipp C."},{"first_name":"Tomasz M.","full_name":"Kulinski, Tomasz M.","last_name":"Kulinski"},{"first_name":"Hans-Christian","last_name":"Theussl","full_name":"Theussl, Hans-Christian"},{"full_name":"Shimizu, Takahiko","last_name":"Shimizu","first_name":"Takahiko"},{"first_name":"Josef M.","last_name":"Penninger","full_name":"Penninger, Josef M."},{"orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","last_name":"Pauler","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Quanah J.","full_name":"Hudson, Quanah J.","last_name":"Hudson"}],"citation":{"mla":"Andergassen, Daniel, et al. “The Airn LncRNA Does Not Require Any DNA Elements within Its Locus to Silence Distant Imprinted Genes.” <i>PLoS Genetics</i>, vol. 15, no. 7, e1008268, Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1008268\">10.1371/journal.pgen.1008268</a>.","ama":"Andergassen D, Muckenhuber M, Bammer PC, et al. The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes. <i>PLoS Genetics</i>. 2019;15(7). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1008268\">10.1371/journal.pgen.1008268</a>","ista":"Andergassen D, Muckenhuber M, Bammer PC, Kulinski TM, Theussl H-C, Shimizu T, Penninger JM, Pauler F, Hudson QJ. 2019. The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes. PLoS Genetics. 15(7), e1008268.","short":"D. Andergassen, M. Muckenhuber, P.C. Bammer, T.M. Kulinski, H.-C. Theussl, T. Shimizu, J.M. Penninger, F. Pauler, Q.J. Hudson, PLoS Genetics 15 (2019).","apa":"Andergassen, D., Muckenhuber, M., Bammer, P. C., Kulinski, T. M., Theussl, H.-C., Shimizu, T., … Hudson, Q. J. (2019). The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes. <i>PLoS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1008268\">https://doi.org/10.1371/journal.pgen.1008268</a>","ieee":"D. Andergassen <i>et al.</i>, “The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes,” <i>PLoS Genetics</i>, vol. 15, no. 7. Public Library of Science, 2019.","chicago":"Andergassen, Daniel, Markus Muckenhuber, Philipp C. Bammer, Tomasz M. Kulinski, Hans-Christian Theussl, Takahiko Shimizu, Josef M. Penninger, Florian Pauler, and Quanah J. Hudson. “The Airn LncRNA Does Not Require Any DNA Elements within Its Locus to Silence Distant Imprinted Genes.” <i>PLoS Genetics</i>. Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pgen.1008268\">https://doi.org/10.1371/journal.pgen.1008268</a>."},"publication_status":"published","ddc":["570"],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"isi":1,"article_number":"e1008268","title":"The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes","external_id":{"pmid":["31329595"],"isi":["000478689100025"]},"doi":"10.1371/journal.pgen.1008268","year":"2019","publication":"PLoS Genetics","issue":"7","file_date_updated":"2020-07-14T12:47:57Z","intvolume":"        15","status":"public","day":"22","type":"journal_article","date_created":"2020-01-29T16:14:07Z","file":[{"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_id":"7446","file_name":"2019_PlosGenetics_Andergassen.pdf","file_size":2302307,"date_created":"2020-02-04T10:11:55Z","checksum":"2f51fc91e4a4199827adc51d432ad864","date_updated":"2020-07-14T12:47:57Z","access_level":"open_access"}],"has_accepted_license":"1","department":[{"_id":"SiHi"}],"scopus_import":"1","publisher":"Public Library of Science","language":[{"iso":"eng"}],"month":"07","date_published":"2019-07-22T00:00:00Z","article_type":"original"},{"ddc":["570"],"isi":1,"article_number":"e1007698","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"external_id":{"isi":["000449328500025"]},"title":"Genome amplification and cellular senescence are hallmarks of human placenta development","doi":"10.1371/journal.pgen.1007698","year":"2018","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","quality_controlled":"1","_id":"5998","publication_identifier":{"issn":["1553-7404"]},"oa":1,"date_updated":"2023-09-19T14:31:43Z","volume":14,"article_processing_charge":"No","author":[{"orcid":"0000-0002-2340-7431","last_name":"Velicky","full_name":"Velicky, Philipp","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gudrun","last_name":"Meinhardt","full_name":"Meinhardt, Gudrun"},{"first_name":"Kerstin","full_name":"Plessl, Kerstin","last_name":"Plessl"},{"first_name":"Sigrid","last_name":"Vondra","full_name":"Vondra, Sigrid"},{"last_name":"Weiss","full_name":"Weiss, Tamara","first_name":"Tamara"},{"full_name":"Haslinger, Peter","last_name":"Haslinger","first_name":"Peter"},{"full_name":"Lendl, Thomas","last_name":"Lendl","first_name":"Thomas"},{"first_name":"Karin","last_name":"Aumayr","full_name":"Aumayr, Karin"},{"first_name":"Mario","full_name":"Mairhofer, Mario","last_name":"Mairhofer"},{"first_name":"Xiaowei","full_name":"Zhu, Xiaowei","last_name":"Zhu"},{"first_name":"Birgit","full_name":"Schütz, Birgit","last_name":"Schütz"},{"last_name":"Hannibal","full_name":"Hannibal, Roberta L.","first_name":"Roberta L."},{"full_name":"Lindau, Robert","last_name":"Lindau","first_name":"Robert"},{"first_name":"Beatrix","full_name":"Weil, Beatrix","last_name":"Weil"},{"first_name":"Jan","full_name":"Ernerudh, Jan","last_name":"Ernerudh"},{"full_name":"Neesen, Jürgen","last_name":"Neesen","first_name":"Jürgen"},{"full_name":"Egger, Gerda","last_name":"Egger","first_name":"Gerda"},{"full_name":"Mikula, Mario","last_name":"Mikula","first_name":"Mario"},{"last_name":"Röhrl","full_name":"Röhrl, Clemens","first_name":"Clemens"},{"full_name":"Urban, Alexander E.","last_name":"Urban","first_name":"Alexander E."},{"full_name":"Baker, Julie","last_name":"Baker","first_name":"Julie"},{"full_name":"Knöfler, Martin","last_name":"Knöfler","first_name":"Martin"},{"first_name":"Jürgen","last_name":"Pollheimer","full_name":"Pollheimer, Jürgen"}],"abstract":[{"lang":"eng","text":"Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) β-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM."}],"publication_status":"published","citation":{"chicago":"Velicky, Philipp, Gudrun Meinhardt, Kerstin Plessl, Sigrid Vondra, Tamara Weiss, Peter Haslinger, Thomas Lendl, et al. “Genome Amplification and Cellular Senescence Are Hallmarks of Human Placenta Development.” <i>PLOS Genetics</i>. Public Library of Science, 2018. <a href=\"https://doi.org/10.1371/journal.pgen.1007698\">https://doi.org/10.1371/journal.pgen.1007698</a>.","ieee":"P. Velicky <i>et al.</i>, “Genome amplification and cellular senescence are hallmarks of human placenta development,” <i>PLOS Genetics</i>, vol. 14, no. 10. Public Library of Science, 2018.","apa":"Velicky, P., Meinhardt, G., Plessl, K., Vondra, S., Weiss, T., Haslinger, P., … Pollheimer, J. (2018). Genome amplification and cellular senescence are hallmarks of human placenta development. <i>PLOS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1007698\">https://doi.org/10.1371/journal.pgen.1007698</a>","short":"P. Velicky, G. Meinhardt, K. Plessl, S. Vondra, T. Weiss, P. Haslinger, T. Lendl, K. Aumayr, M. Mairhofer, X. Zhu, B. Schütz, R.L. Hannibal, R. Lindau, B. Weil, J. Ernerudh, J. Neesen, G. Egger, M. Mikula, C. Röhrl, A.E. Urban, J. Baker, M. Knöfler, J. Pollheimer, PLOS Genetics 14 (2018).","ista":"Velicky P, Meinhardt G, Plessl K, Vondra S, Weiss T, Haslinger P, Lendl T, Aumayr K, Mairhofer M, Zhu X, Schütz B, Hannibal RL, Lindau R, Weil B, Ernerudh J, Neesen J, Egger G, Mikula M, Röhrl C, Urban AE, Baker J, Knöfler M, Pollheimer J. 2018. Genome amplification and cellular senescence are hallmarks of human placenta development. PLOS Genetics. 14(10), e1007698.","mla":"Velicky, Philipp, et al. “Genome Amplification and Cellular Senescence Are Hallmarks of Human Placenta Development.” <i>PLOS Genetics</i>, vol. 14, no. 10, e1007698, Public Library of Science, 2018, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1007698\">10.1371/journal.pgen.1007698</a>.","ama":"Velicky P, Meinhardt G, Plessl K, et al. Genome amplification and cellular senescence are hallmarks of human placenta development. <i>PLOS Genetics</i>. 2018;14(10). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1007698\">10.1371/journal.pgen.1007698</a>"},"date_created":"2019-02-14T13:07:45Z","file":[{"creator":"kschuh","file_id":"6000","relation":"main_file","content_type":"application/pdf","checksum":"34aa9a5972f61889c19f18be8ee787a0","date_created":"2019-02-14T13:14:35Z","file_size":4592947,"file_name":"2018_PLOS_Velicky.pdf","access_level":"open_access","date_updated":"2020-07-14T12:47:15Z"}],"department":[{"_id":"JoDa"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"publisher":"Public Library of Science","scopus_import":"1","date_published":"2018-10-12T00:00:00Z","month":"10","file_date_updated":"2020-07-14T12:47:15Z","issue":"10","publication":"PLOS Genetics","status":"public","intvolume":"        14","type":"journal_article","day":"12"},{"publication_status":"published","citation":{"apa":"McLachlan, I. G., Beets, I., de Bono, M., &#38; Heiman, M. G. (2018). A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. <i>PLOS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1007435\">https://doi.org/10.1371/journal.pgen.1007435</a>","ieee":"I. G. McLachlan, I. Beets, M. de Bono, and M. G. Heiman, “A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism,” <i>PLOS Genetics</i>, vol. 14, no. 6. Public Library of Science, 2018.","chicago":"McLachlan, Ian G., Isabel Beets, Mario de Bono, and Maxwell G. Heiman. “A Neuronal MAP Kinase Constrains Growth of a Caenorhabditis Elegans Sensory Dendrite throughout the Life of the Organism.” <i>PLOS Genetics</i>. Public Library of Science, 2018. <a href=\"https://doi.org/10.1371/journal.pgen.1007435\">https://doi.org/10.1371/journal.pgen.1007435</a>.","ama":"McLachlan IG, Beets I, de Bono M, Heiman MG. A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. <i>PLOS Genetics</i>. 2018;14(6). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1007435\">10.1371/journal.pgen.1007435</a>","mla":"McLachlan, Ian G., et al. “A Neuronal MAP Kinase Constrains Growth of a Caenorhabditis Elegans Sensory Dendrite throughout the Life of the Organism.” <i>PLOS Genetics</i>, vol. 14, no. 6, e1007435, Public Library of Science, 2018, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1007435\">10.1371/journal.pgen.1007435</a>.","short":"I.G. McLachlan, I. Beets, M. de Bono, M.G. Heiman, PLOS Genetics 14 (2018).","ista":"McLachlan IG, Beets I, de Bono M, Heiman MG. 2018. A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. PLOS Genetics. 14(6), e1007435."},"author":[{"first_name":"Ian G.","full_name":"McLachlan, Ian G.","last_name":"McLachlan"},{"last_name":"Beets","full_name":"Beets, Isabel","first_name":"Isabel"},{"orcid":"0000-0001-8347-0443","last_name":"de Bono","full_name":"de Bono, Mario","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Maxwell G.","full_name":"Heiman, Maxwell G.","last_name":"Heiman"}],"abstract":[{"lang":"eng","text":"Neurons develop elaborate morphologies that provide a model for understanding cellular architecture. By studying C. elegans sensory dendrites, we previously identified genes that act to promote the extension of ciliated sensory dendrites during embryogenesis. Interestingly, the nonciliated dendrite of the oxygen-sensing neuron URX is not affected by these genes, suggesting it develops through a distinct mechanism. Here, we use a visual forward genetic screen to identify mutants that affect URX dendrite morphogenesis. We find that disruption of the MAP kinase MAPK-15 or the βH-spectrin SMA-1 causes a phenotype opposite to what we had seen before: dendrites extend normally during embryogenesis but begin to overgrow as the animals reach adulthood, ultimately extending up to 150% of their normal length. SMA-1 is broadly expressed and acts non-cell-autonomously, while MAPK-15 is expressed in many sensory neurons including URX and acts cell-autonomously. MAPK-15 acts at the time of overgrowth, localizes at the dendrite ending, and requires its kinase activity, suggesting it acts locally in time and space to constrain dendrite growth. Finally, we find that the oxygen-sensing guanylate cyclase GCY-35, which normally localizes at the dendrite ending, is localized throughout the overgrown region, and that overgrowth can be suppressed by overexpressing GCY-35 or by genetically mimicking elevated cGMP signaling. These results suggest that overgrowth may correspond to expansion of a sensory compartment at the dendrite ending, reminiscent of the remodeling of sensory cilia or dendritic spines. Thus, in contrast to established pathways that promote dendrite growth during early development, our results reveal a distinct mechanism that constrains dendrite growth throughout the life of the animal, possibly by controlling the size of a sensory compartment at the dendrite ending."}],"oa":1,"volume":14,"date_updated":"2021-01-12T08:06:11Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","quality_controlled":"1","_id":"6111","pmid":1,"publication_identifier":{"issn":["1553-7404"]},"extern":"1","year":"2018","doi":"10.1371/journal.pgen.1007435","title":"A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism","external_id":{"pmid":["29879119"]},"article_number":"e1007435","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"type":"journal_article","day":"07","status":"public","intvolume":"        14","file_date_updated":"2020-07-14T12:47:19Z","issue":"6","publication":"PLOS Genetics","date_published":"2018-06-07T00:00:00Z","month":"06","language":[{"iso":"eng"}],"publisher":"Public Library of Science","has_accepted_license":"1","file":[{"file_name":"2018_PLOS_McLachlan.pdf","file_size":13011506,"date_created":"2019-03-19T13:18:01Z","checksum":"622036b945365dbc575bea2768aa9bc8","date_updated":"2020-07-14T12:47:19Z","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_id":"6112","creator":"kschuh"}],"date_created":"2019-03-19T13:09:28Z"},{"title":"Arabidopsis type II phosphatidylinositol 4-kinase PI4Kγ5 regulates auxin biosynthesis and leaf margin development through interacting with membrane-bound transcription factor ANAC078","year":"2016","doi":"10.1371/journal.pgen.1006252","ddc":["580"],"article_number":"e1006252","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"full_name":"Tang, Yong","last_name":"Tang","first_name":"Yong"},{"first_name":"Chun-Yan","full_name":"Zhao, Chun-Yan","last_name":"Zhao"},{"full_name":"Tan, Shutang","last_name":"Tan","orcid":"0000-0002-0471-8285","first_name":"Shutang","id":"2DE75584-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Xue, Hong-Wei","last_name":"Xue","first_name":"Hong-Wei"}],"abstract":[{"lang":"eng","text":"Normal leaf margin development is important for leaf morphogenesis and contributes to diverse leaf shapes in higher plants. We here show the crucial roles of an atypical type II phosphatidylinositol 4-kinase, PI4Kγ5, in Arabidopsis leaf margin development. PI4Kγ5 presents a dynamics expression pattern along with leaf development and a T-DNA mutant lacking PI4Kγ5, pi4kγ5–1, presents serrated leaves, which is resulted from the accelerated cell division and increased auxin concentration at serration tips. Studies revealed that PI4Kγ5 interacts with and phosphorylates a membrane-bound NAC transcription factor, ANAC078. Previous studies demonstrated that membrane-bound transcription factors regulate gene transcription by undergoing proteolytic process to translocate into nucleus, and ANAC078 undergoes proteolysis by cleaving off the transmembrane region and carboxyl terminal. Western blot analysis indeed showed that ANAC078 deleting of carboxyl terminal is significantly reduced in pi4kγ5–1, indicating that PI4Kγ5 is important for the cleavage of ANAC078. This is consistent with the subcellular localization observation showing that fluorescence by GFP-ANAC078 is detected at plasma membrane but not nucleus in pi4kγ5–1 mutant and that expression of ANAC078 deleting of carboxyl terminal, driven by PI4Kγ5 promoter, could rescue the leaf serration defects of pi4kγ5–1. Further analysis showed that ANAC078 suppresses the auxin synthesis by directly binding and regulating the expression of auxin synthesis-related genes. These results indicate that PI4Kγ5 interacts with ANAC078 to negatively regulate auxin synthesis and hence influences cell proliferation and leaf development, providing informative clues for the regulation of in situ auxin synthesis and cell division, as well as the cleavage and functional mechanism of membrane-bound transcription factors."}],"publication_status":"published","citation":{"chicago":"Tang, Yong, Chun-Yan Zhao, Shutang Tan, and Hong-Wei Xue. “Arabidopsis Type II Phosphatidylinositol 4-Kinase PI4Kγ5 Regulates Auxin Biosynthesis and Leaf Margin Development through Interacting with Membrane-Bound Transcription Factor ANAC078.” <i>PLOS Genetics</i>. Public Library of Science, 2016. <a href=\"https://doi.org/10.1371/journal.pgen.1006252\">https://doi.org/10.1371/journal.pgen.1006252</a>.","ieee":"Y. Tang, C.-Y. Zhao, S. Tan, and H.-W. Xue, “Arabidopsis type II phosphatidylinositol 4-kinase PI4Kγ5 regulates auxin biosynthesis and leaf margin development through interacting with membrane-bound transcription factor ANAC078,” <i>PLOS Genetics</i>, vol. 12, no. 8. Public Library of Science, 2016.","apa":"Tang, Y., Zhao, C.-Y., Tan, S., &#38; Xue, H.-W. (2016). Arabidopsis type II phosphatidylinositol 4-kinase PI4Kγ5 regulates auxin biosynthesis and leaf margin development through interacting with membrane-bound transcription factor ANAC078. <i>PLOS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1006252\">https://doi.org/10.1371/journal.pgen.1006252</a>","ista":"Tang Y, Zhao C-Y, Tan S, Xue H-W. 2016. Arabidopsis type II phosphatidylinositol 4-kinase PI4Kγ5 regulates auxin biosynthesis and leaf margin development through interacting with membrane-bound transcription factor ANAC078. PLOS Genetics. 12(8), e1006252.","short":"Y. Tang, C.-Y. Zhao, S. Tan, H.-W. Xue, PLOS Genetics 12 (2016).","ama":"Tang Y, Zhao C-Y, Tan S, Xue H-W. Arabidopsis type II phosphatidylinositol 4-kinase PI4Kγ5 regulates auxin biosynthesis and leaf margin development through interacting with membrane-bound transcription factor ANAC078. <i>PLOS Genetics</i>. 2016;12(8). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1006252\">10.1371/journal.pgen.1006252</a>","mla":"Tang, Yong, et al. “Arabidopsis Type II Phosphatidylinositol 4-Kinase PI4Kγ5 Regulates Auxin Biosynthesis and Leaf Margin Development through Interacting with Membrane-Bound Transcription Factor ANAC078.” <i>PLOS Genetics</i>, vol. 12, no. 8, e1006252, Public Library of Science, 2016, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1006252\">10.1371/journal.pgen.1006252</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","quality_controlled":"1","_id":"7599","extern":"1","publication_identifier":{"issn":["1553-7404"]},"oa":1,"date_updated":"2021-01-12T08:14:25Z","volume":12,"article_processing_charge":"No","language":[{"iso":"eng"}],"publisher":"Public Library of Science","date_published":"2016-08-16T00:00:00Z","article_type":"original","month":"08","file":[{"checksum":"ff0ab9a6bed11cda800a6e59820866a0","date_created":"2020-03-23T12:15:31Z","file_size":3266119,"file_name":"2016_PlosGenetics_Tang.PDF","access_level":"open_access","date_updated":"2020-07-14T12:48:01Z","creator":"dernst","file_id":"7612","relation":"main_file","content_type":"application/pdf"}],"date_created":"2020-03-21T16:08:33Z","has_accepted_license":"1","status":"public","intvolume":"        12","type":"journal_article","day":"16","file_date_updated":"2020-07-14T12:48:01Z","issue":"8","publication":"PLOS Genetics"},{"external_id":{"pmid":["24603482"]},"title":"An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism","doi":"10.1371/journal.pgen.1004082","year":"2014","ddc":["570"],"article_number":"e1004082","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"full_name":"Chen, Changchun","last_name":"Chen","first_name":"Changchun"},{"first_name":"Eisuke","full_name":"Itakura, Eisuke","last_name":"Itakura"},{"last_name":"Weber","full_name":"Weber, Katherine P.","first_name":"Katherine P."},{"first_name":"Ramanujan S.","last_name":"Hegde","full_name":"Hegde, Ramanujan S."},{"id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","full_name":"de Bono, Mario","last_name":"de Bono","orcid":"0000-0001-8347-0443","first_name":"Mario"}],"abstract":[{"text":"Despite the importance of G-protein coupled receptors (GPCRs) their biogenesis is poorly understood. Like vertebrates, C. elegans uses a large family of GPCRs as chemoreceptors. A subset of these receptors, such as ODR-10, requires the odr-4 and odr-8 genes to be appropriately localized to sensory cilia. The odr-4 gene encodes a conserved tail-anchored transmembrane protein; the molecular identity of odr-8 is unknown. Here, we show that odr-8 encodes the C. elegans ortholog of Ufm1-specific protease 2 (UfSP2). UfSPs are cysteine proteases identified biochemically by their ability to liberate the ubiquitin-like modifier Ufm1 from its pro-form and protein conjugates. ODR-8/UfSP2 and ODR-4 are expressed in the same set of twelve chemosensory neurons, and physically interact at the ER membrane. ODR-4 also binds ODR-10, suggesting that an ODR-4/ODR-8 complex promotes GPCR folding, maturation, or export from the ER. The physical interaction between human ODR4 and UfSP2 suggests that this complex's role in GPCR biogenesis may be evolutionarily conserved. Unexpectedly, mutant versions of ODR-8/UfSP2 lacking catalytic residues required for protease activity can rescue all odr-8 mutant phenotypes tested. Moreover, deleting C. elegans ufm-1 does not alter chemoreceptor traffic to cilia, either in wild type or in odr-8 mutants. Thus, UfSP2 proteins have protease- and Ufm1-independent functions in GPCR biogenesis.","lang":"eng"}],"publication_status":"published","citation":{"ista":"Chen C, Itakura E, Weber KP, Hegde RS, de Bono M. 2014. An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism. PLoS Genetics. 10(3), e1004082.","short":"C. Chen, E. Itakura, K.P. Weber, R.S. Hegde, M. de Bono, PLoS Genetics 10 (2014).","mla":"Chen, Changchun, et al. “An ER Complex of ODR-4 and ODR-8/Ufm1 Specific Protease 2 Promotes GPCR Maturation by a Ufm1-Independent Mechanism.” <i>PLoS Genetics</i>, vol. 10, no. 3, e1004082, Public Library of Science (PLoS), 2014, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1004082\">10.1371/journal.pgen.1004082</a>.","ama":"Chen C, Itakura E, Weber KP, Hegde RS, de Bono M. An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism. <i>PLoS Genetics</i>. 2014;10(3). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1004082\">10.1371/journal.pgen.1004082</a>","chicago":"Chen, Changchun, Eisuke Itakura, Katherine P. Weber, Ramanujan S. Hegde, and Mario de Bono. “An ER Complex of ODR-4 and ODR-8/Ufm1 Specific Protease 2 Promotes GPCR Maturation by a Ufm1-Independent Mechanism.” <i>PLoS Genetics</i>. Public Library of Science (PLoS), 2014. <a href=\"https://doi.org/10.1371/journal.pgen.1004082\">https://doi.org/10.1371/journal.pgen.1004082</a>.","apa":"Chen, C., Itakura, E., Weber, K. P., Hegde, R. S., &#38; de Bono, M. (2014). An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism. <i>PLoS Genetics</i>. Public Library of Science (PLoS). <a href=\"https://doi.org/10.1371/journal.pgen.1004082\">https://doi.org/10.1371/journal.pgen.1004082</a>","ieee":"C. Chen, E. Itakura, K. P. Weber, R. S. Hegde, and M. de Bono, “An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism,” <i>PLoS Genetics</i>, vol. 10, no. 3. Public Library of Science (PLoS), 2014."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","quality_controlled":"1","pmid":1,"_id":"6124","publication_identifier":{"issn":["1553-7404"]},"extern":"1","date_updated":"2021-01-12T08:06:14Z","volume":10,"oa":1,"language":[{"iso":"eng"}],"publisher":"Public Library of Science (PLoS)","date_published":"2014-03-06T00:00:00Z","month":"03","file":[{"file_name":"2014_PLOS_Chen.PDF","file_size":8286819,"date_created":"2019-03-19T14:50:07Z","checksum":"ac19941089a4262bb5bd74434a08b003","date_updated":"2020-07-14T12:47:20Z","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_id":"6125","creator":"kschuh"}],"date_created":"2019-03-19T14:45:56Z","has_accepted_license":"1","status":"public","intvolume":"        10","type":"journal_article","day":"06","file_date_updated":"2020-07-14T12:47:20Z","issue":"3","publication":"PLoS Genetics"},{"external_id":{"pmid":["23468646"]},"title":"Dynamic association of NUP98 with the human genome","doi":"10.1371/journal.pgen.1003308","year":"2013","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1371/journal.pgen.1003308"}],"article_number":"e1003308","abstract":[{"lang":"eng","text":"Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors, histone-modification enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins, well known components that control nucleo-cytoplasmic trafficking, have wide-ranging functions in developmental gene regulation that potentially extend beyond their role in nuclear transport. Whether the unexpected role of nuclear pore proteins in transcription regulation, which initially has been described in fungi and flies, also applies to human cells is unknown. Here we show at a genome-wide level that the nuclear pore protein NUP98 associates with developmentally regulated genes active during human embryonic stem cell differentiation. Overexpression of a dominant negative fragment of NUP98 levels decreases expression levels of NUP98-bound genes. In addition, we identify two modes of developmental gene regulation by NUP98 that are differentiated by the spatial localization of NUP98 target genes. Genes in the initial stage of developmental induction can associate with NUP98 that is embedded in the nuclear pores at the nuclear periphery. Alternatively, genes that are highly induced can interact with NUP98 in the nuclear interior, away from the nuclear pores. This work demonstrates for the first time that NUP98 dynamically associates with the human genome during differentiation, revealing a role of a nuclear pore protein in regulating developmental gene expression programs."}],"author":[{"first_name":"Yun","full_name":"Liang, Yun","last_name":"Liang"},{"last_name":"Franks","full_name":"Franks, Tobias M.","first_name":"Tobias M."},{"first_name":"Maria C.","last_name":"Marchetto","full_name":"Marchetto, Maria C."},{"first_name":"Fred H.","full_name":"Gage, Fred H.","last_name":"Gage"},{"id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W","last_name":"HETZER"}],"keyword":["Cancer Research","Genetics (clinical)","Genetics","Molecular Biology","Ecology","Evolution","Behavior and Systematics"],"publication_status":"published","citation":{"ista":"Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer M. 2013. Dynamic association of NUP98 with the human genome. PLoS Genetics. 9(2), e1003308.","short":"Y. Liang, T.M. Franks, M.C. Marchetto, F.H. Gage, M. Hetzer, PLoS Genetics 9 (2013).","mla":"Liang, Yun, et al. “Dynamic Association of NUP98 with the Human Genome.” <i>PLoS Genetics</i>, vol. 9, no. 2, e1003308, Public Library of Science, 2013, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1003308\">10.1371/journal.pgen.1003308</a>.","ama":"Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer M. Dynamic association of NUP98 with the human genome. <i>PLoS Genetics</i>. 2013;9(2). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1003308\">10.1371/journal.pgen.1003308</a>","chicago":"Liang, Yun, Tobias M. Franks, Maria C. Marchetto, Fred H. Gage, and Martin Hetzer. “Dynamic Association of NUP98 with the Human Genome.” <i>PLoS Genetics</i>. Public Library of Science, 2013. <a href=\"https://doi.org/10.1371/journal.pgen.1003308\">https://doi.org/10.1371/journal.pgen.1003308</a>.","ieee":"Y. Liang, T. M. Franks, M. C. Marchetto, F. H. Gage, and M. Hetzer, “Dynamic association of NUP98 with the human genome,” <i>PLoS Genetics</i>, vol. 9, no. 2. Public Library of Science, 2013.","apa":"Liang, Y., Franks, T. M., Marchetto, M. C., Gage, F. H., &#38; Hetzer, M. (2013). Dynamic association of NUP98 with the human genome. <i>PLoS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1003308\">https://doi.org/10.1371/journal.pgen.1003308</a>"},"pmid":1,"_id":"11086","extern":"1","publication_identifier":{"issn":["1553-7404"]},"user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","quality_controlled":"1","oa_version":"Published Version","date_updated":"2022-07-18T08:45:58Z","volume":9,"oa":1,"article_processing_charge":"No","publisher":"Public Library of Science","scopus_import":"1","language":[{"iso":"eng"}],"month":"02","article_type":"original","date_published":"2013-02-28T00:00:00Z","date_created":"2022-04-07T07:50:59Z","intvolume":"         9","status":"public","day":"28","type":"journal_article","issue":"2","publication":"PLoS Genetics"},{"publication_status":"published","citation":{"chicago":"Kodama-Namba, Eiji, Lorenz A. Fenk, Andrew J. Bretscher, Einav Gross, K. Emanuel Busch, and Mario de Bono. “Cross-Modulation of Homeostatic Responses to Temperature, Oxygen and Carbon Dioxide in C. Elegans.” <i>PLoS Genetics</i>. Public Library of Science (PLoS), 2013. <a href=\"https://doi.org/10.1371/journal.pgen.1004011\">https://doi.org/10.1371/journal.pgen.1004011</a>.","ieee":"E. Kodama-Namba, L. A. Fenk, A. J. Bretscher, E. Gross, K. E. Busch, and M. de Bono, “Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans,” <i>PLoS Genetics</i>, vol. 9, no. 12. Public Library of Science (PLoS), 2013.","apa":"Kodama-Namba, E., Fenk, L. A., Bretscher, A. J., Gross, E., Busch, K. E., &#38; de Bono, M. (2013). Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans. <i>PLoS Genetics</i>. Public Library of Science (PLoS). <a href=\"https://doi.org/10.1371/journal.pgen.1004011\">https://doi.org/10.1371/journal.pgen.1004011</a>","short":"E. Kodama-Namba, L.A. Fenk, A.J. Bretscher, E. Gross, K.E. Busch, M. de Bono, PLoS Genetics 9 (2013).","ista":"Kodama-Namba E, Fenk LA, Bretscher AJ, Gross E, Busch KE, de Bono M. 2013. Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans. PLoS Genetics. 9(12), e1004011.","ama":"Kodama-Namba E, Fenk LA, Bretscher AJ, Gross E, Busch KE, de Bono M. Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans. <i>PLoS Genetics</i>. 2013;9(12). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1004011\">10.1371/journal.pgen.1004011</a>","mla":"Kodama-Namba, Eiji, et al. “Cross-Modulation of Homeostatic Responses to Temperature, Oxygen and Carbon Dioxide in C. Elegans.” <i>PLoS Genetics</i>, vol. 9, no. 12, e1004011, Public Library of Science (PLoS), 2013, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1004011\">10.1371/journal.pgen.1004011</a>."},"abstract":[{"text":"Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O2 and CO2. CO2 is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO2 changes. CO2 evokes distinct AFD Ca2+ responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO2 responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO2. Surprisingly, gradients of 0.01% CO2/second evoke very different Ca2+ responses from gradients of 0.04% CO2/second. Ambient O2 provides further contextual modulation of CO2 avoidance. At 21% O2 tonic signalling from the O2-sensing neuron URX inhibits CO2 avoidance. This inhibition can be graded according to O2 levels. In a natural wild isolate, a switch from 21% to 19% O2 is sufficient to convert CO2 from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O2 on CO2 avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO2-evoked Ca2+ responses. Ambient O2 and acclimation temperature act combinatorially to modulate CO2 responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans.","lang":"eng"}],"author":[{"first_name":"Eiji","last_name":"Kodama-Namba","full_name":"Kodama-Namba, Eiji"},{"first_name":"Lorenz A.","last_name":"Fenk","full_name":"Fenk, Lorenz A."},{"first_name":"Andrew J.","full_name":"Bretscher, Andrew J.","last_name":"Bretscher"},{"full_name":"Gross, Einav","last_name":"Gross","first_name":"Einav"},{"last_name":"Busch","full_name":"Busch, K. Emanuel","first_name":"K. Emanuel"},{"id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","first_name":"Mario","full_name":"de Bono, Mario","last_name":"de Bono","orcid":"0000-0001-8347-0443"}],"oa":1,"date_updated":"2021-01-12T08:06:15Z","volume":9,"_id":"6128","pmid":1,"extern":"1","publication_identifier":{"issn":["1553-7404"]},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","oa_version":"Published Version","doi":"10.1371/journal.pgen.1004011","year":"2013","title":"Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans","external_id":{"pmid":["24385919"]},"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"e1004011","ddc":["570"],"day":"19","type":"journal_article","intvolume":"         9","status":"public","issue":"12","publication":"PLoS Genetics","file_date_updated":"2020-07-14T12:47:20Z","month":"12","date_published":"2013-12-19T00:00:00Z","publisher":"Public Library of Science (PLoS)","language":[{"iso":"eng"}],"has_accepted_license":"1","date_created":"2019-03-19T14:58:51Z","file":[{"date_created":"2019-03-19T15:14:51Z","checksum":"299b6321be79931c7c17c5db6e69c711","file_name":"2013_PLOS_Kodama-Namba.PDF","file_size":4499039,"date_updated":"2020-07-14T12:47:20Z","access_level":"open_access","file_id":"6129","creator":"kschuh","content_type":"application/pdf","relation":"main_file"}]},{"date_published":"2011-03-17T00:00:00Z","month":"03","language":[{"iso":"eng"}],"publisher":"Public Library of Science","has_accepted_license":"1","file":[{"creator":"kschuh","file_id":"6141","relation":"main_file","content_type":"application/pdf","checksum":"c609b2ce616d7dafbb617ec5d022f1ea","date_created":"2019-03-20T15:18:11Z","file_size":5625063,"file_name":"2011_PLOS_Arellano-Carbajal.PDF","access_level":"open_access","date_updated":"2020-07-14T12:47:20Z"}],"date_created":"2019-03-20T15:08:23Z","type":"journal_article","day":"17","status":"public","intvolume":"         7","file_date_updated":"2020-07-14T12:47:20Z","issue":"3","publication":"PLoS Genetics","doi":"10.1371/journal.pgen.1001341","year":"2011","title":"Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability","external_id":{"pmid":["21437263"]},"article_number":"e1001341","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"publication_status":"published","citation":{"chicago":"Arellano-Carbajal, Fausto, Luis Briseño-Roa, Africa Couto, Benny H. H. Cheung, Michel Labouesse, and Mario de Bono. “Macoilin, a Conserved Nervous System–Specific ER Membrane Protein That Regulates Neuronal Excitability.” <i>PLoS Genetics</i>. Public Library of Science, 2011. <a href=\"https://doi.org/10.1371/journal.pgen.1001341\">https://doi.org/10.1371/journal.pgen.1001341</a>.","ieee":"F. Arellano-Carbajal, L. Briseño-Roa, A. Couto, B. H. H. Cheung, M. Labouesse, and M. de Bono, “Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability,” <i>PLoS Genetics</i>, vol. 7, no. 3. Public Library of Science, 2011.","apa":"Arellano-Carbajal, F., Briseño-Roa, L., Couto, A., Cheung, B. H. H., Labouesse, M., &#38; de Bono, M. (2011). Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability. <i>PLoS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1001341\">https://doi.org/10.1371/journal.pgen.1001341</a>","short":"F. Arellano-Carbajal, L. Briseño-Roa, A. Couto, B.H.H. Cheung, M. Labouesse, M. de Bono, PLoS Genetics 7 (2011).","ista":"Arellano-Carbajal F, Briseño-Roa L, Couto A, Cheung BHH, Labouesse M, de Bono M. 2011. Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability. PLoS Genetics. 7(3), e1001341.","ama":"Arellano-Carbajal F, Briseño-Roa L, Couto A, Cheung BHH, Labouesse M, de Bono M. Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability. <i>PLoS Genetics</i>. 2011;7(3). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1001341\">10.1371/journal.pgen.1001341</a>","mla":"Arellano-Carbajal, Fausto, et al. “Macoilin, a Conserved Nervous System–Specific ER Membrane Protein That Regulates Neuronal Excitability.” <i>PLoS Genetics</i>, vol. 7, no. 3, e1001341, Public Library of Science, 2011, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1001341\">10.1371/journal.pgen.1001341</a>."},"author":[{"full_name":"Arellano-Carbajal, Fausto","last_name":"Arellano-Carbajal","first_name":"Fausto"},{"first_name":"Luis","last_name":"Briseño-Roa","full_name":"Briseño-Roa, Luis"},{"full_name":"Couto, Africa","last_name":"Couto","first_name":"Africa"},{"last_name":"Cheung","full_name":"Cheung, Benny H. H.","first_name":"Benny H. H."},{"full_name":"Labouesse, Michel","last_name":"Labouesse","first_name":"Michel"},{"last_name":"de Bono","full_name":"de Bono, Mario","orcid":"0000-0001-8347-0443","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"text":"Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O2 responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca2+ transients, at least in some neurons: in maco-1 mutants the O2-sensing neuron PQR is unable to generate a Ca2+ response to a rise in O2. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O2, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca2+ channels, also fails to disrupt Ca2+ responses in the PQR cell body to O2 stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca2+ channel α1 subunit, recapitulate the Ca2+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or traffic of ion channels or ion channel regulators.","lang":"eng"}],"volume":7,"oa":1,"date_updated":"2021-01-12T08:06:19Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","oa_version":"Published Version","_id":"6140","pmid":1,"extern":"1","publication_identifier":{"issn":["1553-7404"]}}]