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PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry
Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589783/ https://www.ncbi.nlm.nih.gov/pubmed/30840554 http://dx.doi.org/10.1091/mbc.E18-10-0631 |
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author | Boudreau, Vincent Chen, Richard Edwards, Alan Sulaimain, Muhammad Maddox, Paul S. |
author_facet | Boudreau, Vincent Chen, Richard Edwards, Alan Sulaimain, Muhammad Maddox, Paul S. |
author_sort | Boudreau, Vincent |
collection | PubMed |
description | Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators, including protein phosphatase 2A (PP2A-B55/SUR-6), biophysical regulators, including dynein, and the nuclear lamina is unclear. Here, we uncover a role for PP2A-B55/SUR-6 in regulating centrosome separation. Mechanistically, PP2A-B55/SUR-6 regulates nuclear size before mitotic entry, in turn affecting nuclear envelope–based dynein density and motor capacity. Computational simulations predicted the requirement of PP2A-B55/SUR-6 regulation of nuclear size and nuclear-envelope dynein density for proper centrosome separation. Conversely, compromising nuclear lamina integrity led to centrosome detachment from the nuclear envelope and migration defects. Removal of PP2A-B55/SUR-6 and the nuclear lamina simultaneously further disrupted centrosome separation, leading to unseparated centrosome pairs dissociated from the nuclear envelope. Taking these combined results into consideration, we propose a model in which centrosomes migrate and are positioned through the concerted action of PP2A-B55/SUR-6–regulated nuclear envelope–based dynein pulling forces and centrosome–nuclear envelope tethering. Our results add critical precision to models of centrosome separation relative to the nucleus during spindle formation in cell division. |
format | Online Article Text |
id | pubmed-6589783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65897832019-07-02 PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry Boudreau, Vincent Chen, Richard Edwards, Alan Sulaimain, Muhammad Maddox, Paul S. Mol Biol Cell Articles Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators, including protein phosphatase 2A (PP2A-B55/SUR-6), biophysical regulators, including dynein, and the nuclear lamina is unclear. Here, we uncover a role for PP2A-B55/SUR-6 in regulating centrosome separation. Mechanistically, PP2A-B55/SUR-6 regulates nuclear size before mitotic entry, in turn affecting nuclear envelope–based dynein density and motor capacity. Computational simulations predicted the requirement of PP2A-B55/SUR-6 regulation of nuclear size and nuclear-envelope dynein density for proper centrosome separation. Conversely, compromising nuclear lamina integrity led to centrosome detachment from the nuclear envelope and migration defects. Removal of PP2A-B55/SUR-6 and the nuclear lamina simultaneously further disrupted centrosome separation, leading to unseparated centrosome pairs dissociated from the nuclear envelope. Taking these combined results into consideration, we propose a model in which centrosomes migrate and are positioned through the concerted action of PP2A-B55/SUR-6–regulated nuclear envelope–based dynein pulling forces and centrosome–nuclear envelope tethering. Our results add critical precision to models of centrosome separation relative to the nucleus during spindle formation in cell division. The American Society for Cell Biology 2019-03-21 /pmc/articles/PMC6589783/ /pubmed/30840554 http://dx.doi.org/10.1091/mbc.E18-10-0631 Text en © 2019 Boudreau et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Boudreau, Vincent Chen, Richard Edwards, Alan Sulaimain, Muhammad Maddox, Paul S. PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
title | PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
title_full | PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
title_fullStr | PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
title_full_unstemmed | PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
title_short | PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
title_sort | pp2a-b55/sur-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589783/ https://www.ncbi.nlm.nih.gov/pubmed/30840554 http://dx.doi.org/10.1091/mbc.E18-10-0631 |
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