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Active Ran regulates anillin function during cytokinesis
Cytokinesis cleaves a cell into two daughters at the end of mitosis, and must be spatially coordinated with chromosome segregation to prevent aneuploidy. The dogma is that the mitotic spindle governs the assembly and constriction of an actomyosin ring. Here, we reveal a function for active Ran in sp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683762/ https://www.ncbi.nlm.nih.gov/pubmed/28931593 http://dx.doi.org/10.1091/mbc.E17-04-0253 |
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author | Beaudet, Daniel Akhshi, Tara Phillipp, Julia Law, Christopher Piekny, Alisa |
author_facet | Beaudet, Daniel Akhshi, Tara Phillipp, Julia Law, Christopher Piekny, Alisa |
author_sort | Beaudet, Daniel |
collection | PubMed |
description | Cytokinesis cleaves a cell into two daughters at the end of mitosis, and must be spatially coordinated with chromosome segregation to prevent aneuploidy. The dogma is that the mitotic spindle governs the assembly and constriction of an actomyosin ring. Here, we reveal a function for active Ran in spatially restricting the ring. Our model is that during anaphase, “free” importins, whose gradient inversely correlates with active Ran and chromatin position, function as a molecular ruler for the recruitment and localization of anillin, a contractile protein and a crucial regulator of cytokinesis. We found that decreasing Ran-GTP levels or tethering active Ran to the equatorial membrane affects anillin’s localization and causes cytokinesis phenotypes. Anillin contains a conserved nuclear localization signal (NLS) at its C-terminus that binds to importin-β and is required for cortical polarity and cytokinesis. Mutating the NLS decreases anillin’s cortical affinity, causing it to be more dominantly regulated by microtubules. Anillin contains a RhoA-GTP binding domain, which autoinhibits the NLS and the neighboring microtubule-binding domain, and RhoA-GTP binding may relieve this inhibition during mitosis. Retention of the C-terminal NLS in anillin homologues suggests that this is a conserved mechanism for controlling anillin function. |
format | Online Article Text |
id | pubmed-5683762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-56837622018-01-30 Active Ran regulates anillin function during cytokinesis Beaudet, Daniel Akhshi, Tara Phillipp, Julia Law, Christopher Piekny, Alisa Mol Biol Cell Articles Cytokinesis cleaves a cell into two daughters at the end of mitosis, and must be spatially coordinated with chromosome segregation to prevent aneuploidy. The dogma is that the mitotic spindle governs the assembly and constriction of an actomyosin ring. Here, we reveal a function for active Ran in spatially restricting the ring. Our model is that during anaphase, “free” importins, whose gradient inversely correlates with active Ran and chromatin position, function as a molecular ruler for the recruitment and localization of anillin, a contractile protein and a crucial regulator of cytokinesis. We found that decreasing Ran-GTP levels or tethering active Ran to the equatorial membrane affects anillin’s localization and causes cytokinesis phenotypes. Anillin contains a conserved nuclear localization signal (NLS) at its C-terminus that binds to importin-β and is required for cortical polarity and cytokinesis. Mutating the NLS decreases anillin’s cortical affinity, causing it to be more dominantly regulated by microtubules. Anillin contains a RhoA-GTP binding domain, which autoinhibits the NLS and the neighboring microtubule-binding domain, and RhoA-GTP binding may relieve this inhibition during mitosis. Retention of the C-terminal NLS in anillin homologues suggests that this is a conserved mechanism for controlling anillin function. The American Society for Cell Biology 2017-11-15 /pmc/articles/PMC5683762/ /pubmed/28931593 http://dx.doi.org/10.1091/mbc.E17-04-0253 Text en © 2017 Beaudet, Akhshi, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Beaudet, Daniel Akhshi, Tara Phillipp, Julia Law, Christopher Piekny, Alisa Active Ran regulates anillin function during cytokinesis |
title | Active Ran regulates anillin function during cytokinesis |
title_full | Active Ran regulates anillin function during cytokinesis |
title_fullStr | Active Ran regulates anillin function during cytokinesis |
title_full_unstemmed | Active Ran regulates anillin function during cytokinesis |
title_short | Active Ran regulates anillin function during cytokinesis |
title_sort | active ran regulates anillin function during cytokinesis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683762/ https://www.ncbi.nlm.nih.gov/pubmed/28931593 http://dx.doi.org/10.1091/mbc.E17-04-0253 |
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