Cargando…

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Boudreau, Vincent, Chen, Richard, Edwards, Alan, Sulaimain, Muhammad, Maddox, Paul S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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
_version_ 1783429438525931520
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
work_keys_str_mv AT boudreauvincent pp2ab55sur6collaborateswiththenuclearlaminaforcentrosomeseparationduringmitoticentry
AT chenrichard pp2ab55sur6collaborateswiththenuclearlaminaforcentrosomeseparationduringmitoticentry
AT edwardsalan pp2ab55sur6collaborateswiththenuclearlaminaforcentrosomeseparationduringmitoticentry
AT sulaimainmuhammad pp2ab55sur6collaborateswiththenuclearlaminaforcentrosomeseparationduringmitoticentry
AT maddoxpauls pp2ab55sur6collaborateswiththenuclearlaminaforcentrosomeseparationduringmitoticentry