{"external_id":{"pmid":["36201522"]},"year":"2022","quality_controlled":"1","abstract":[{"lang":"eng","text":"A cell’s size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate “unwanted” cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical “lethal” size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the “cell death abnormal” phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell’s commitment to the cell death fate."}],"author":[{"full_name":"Sethi, Aditya","first_name":"Aditya","last_name":"Sethi"},{"last_name":"Wei","first_name":"Hai","full_name":"Wei, Hai"},{"full_name":"Mishra, Nikhil","id":"C4D70E82-1081-11EA-B3ED-9A4C3DDC885E","first_name":"Nikhil","orcid":"0000-0002-6425-5788","last_name":"Mishra"},{"last_name":"Segos","first_name":"Ioannis","full_name":"Segos, Ioannis"},{"full_name":"Lambie, Eric J.","first_name":"Eric J.","last_name":"Lambie"},{"full_name":"Zanin, Esther","first_name":"Esther","last_name":"Zanin"},{"full_name":"Conradt, Barbara","first_name":"Barbara","last_name":"Conradt"}],"publisher":"Public Library of Science","publication_status":"published","publication":"PLOS Biology","_id":"17066","language":[{"iso":"eng"}],"pmid":1,"status":"public","date_created":"2024-05-29T06:09:34Z","file_date_updated":"2024-08-06T07:07:52Z","oa_version":"Published Version","ddc":["570"],"month":"10","article_type":"original","license":"https://creativecommons.org/licenses/by/4.0/","type":"journal_article","volume":20,"department":[{"_id":"CaHe"}],"acknowledgement":"We thank members of the Conradt, Lambie, and Hajnal labs for discussions and comments on the manuscript. We thank M. Bauer, L. Jocham, N. Lebedeva, and L. McGuinness for excellent technical support; A. Hajnal and T. Kohlbrenner (University of Zurich, Switzerland) for allele zh135; and H.R. Horvitz (Massachusetts of Technology, USA) for plasmid pET-CED-3.\r\nSome strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (https://orip.nih.gov/) (P40 OD010440). This work was supported by UCL (Capital Equipment Fund, CEF2), a predoctoral fellowship from the China Scholarship Council (https://www.csc.edu.cn/) to HW, a predoctoral fellowship from the Studienstiftung des Deutschen Volkes (https://www.studienstiftung.de/) to NM, a Wolfson Fellowship from the Royal Society (https://royalsociety.org/) to BC (RSWF\\R1\\180008), the Deutsche Forschungsgemeinschaft (https://www.dfg.de/en/index.jsp) (ZA619/3-1 and ZA619/3-2 to EZ; C0204/10-1 and EXC114 to BC), and the Biotechnology and Biological Sciences Research Council (https://bbsrc.ukri.org/) (BB/V007572/1 to BC). ","publication_identifier":{"issn":["1545-7885"]},"title":"A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans","issue":"10","scopus_import":"1","intvolume":"        20","oa":1,"has_accepted_license":"1","date_updated":"2024-08-06T07:08:54Z","article_number":"e3001786","file":[{"content_type":"application/pdf","checksum":"a7b46460b7819c196028481cc18a7c85","access_level":"open_access","file_id":"17399","creator":"dernst","file_name":"2022_PlosBio_Sethi.pdf","relation":"main_file","success":1,"date_created":"2024-08-06T07:07:52Z","date_updated":"2024-08-06T07:07:52Z","file_size":2515388}],"citation":{"short":"A. Sethi, H. Wei, N. Mishra, I. Segos, E.J. Lambie, E. Zanin, B. Conradt, PLOS Biology 20 (2022).","ieee":"A. Sethi <i>et al.</i>, “A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans,” <i>PLOS Biology</i>, vol. 20, no. 10. Public Library of Science, 2022.","ista":"Sethi A, Wei H, Mishra N, Segos I, Lambie EJ, Zanin E, Conradt B. 2022. A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans. PLOS Biology. 20(10), e3001786.","ama":"Sethi A, Wei H, Mishra N, et al. A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans. <i>PLOS Biology</i>. 2022;20(10). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001786\">10.1371/journal.pbio.3001786</a>","mla":"Sethi, Aditya, et al. “A Caspase–RhoGEF Axis Contributes to the Cell Size Threshold for Apoptotic Death in Developing Caenorhabditis Elegans.” <i>PLOS Biology</i>, vol. 20, no. 10, e3001786, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001786\">10.1371/journal.pbio.3001786</a>.","apa":"Sethi, A., Wei, H., Mishra, N., Segos, I., Lambie, E. J., Zanin, E., &#38; Conradt, B. (2022). A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans. <i>PLOS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3001786\">https://doi.org/10.1371/journal.pbio.3001786</a>","chicago":"Sethi, Aditya, Hai Wei, Nikhil Mishra, Ioannis Segos, Eric J. Lambie, Esther Zanin, and Barbara Conradt. “A Caspase–RhoGEF Axis Contributes to the Cell Size Threshold for Apoptotic Death in Developing Caenorhabditis Elegans.” <i>PLOS Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pbio.3001786\">https://doi.org/10.1371/journal.pbio.3001786</a>."},"day":"06","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2022-10-06T00:00:00Z","doi":"10.1371/journal.pbio.3001786","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"article_processing_charge":"Yes"}