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Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes

Centrosome separation along the surface of the nucleus at the onset of mitosis is critical for bipolar spindle assembly. Dynein anchored on the nuclear envelope is known to be important for centrosome separation, but it is unclear how nuclear dynein forces are organized in an anisotropic manner to p...

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Detalles Bibliográficos
Autores principales: De Simone, Alessandro, Gönczy, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687019/
https://www.ncbi.nlm.nih.gov/pubmed/28701341
http://dx.doi.org/10.1091/mbc.E16-12-0823
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author De Simone, Alessandro
Gönczy, Pierre
author_facet De Simone, Alessandro
Gönczy, Pierre
author_sort De Simone, Alessandro
collection PubMed
description Centrosome separation along the surface of the nucleus at the onset of mitosis is critical for bipolar spindle assembly. Dynein anchored on the nuclear envelope is known to be important for centrosome separation, but it is unclear how nuclear dynein forces are organized in an anisotropic manner to promote the movement of centrosomes away from each other. Here we use computational simulations of Caenorhabditis elegans embryos to address this fundamental question, testing three potential mechanisms by which nuclear dynein may act. First, our analysis shows that expansion of the nuclear volume per se does not generate nuclear dynein–driven separation forces. Second, we find that steric interactions between microtubules and centrosomes contribute to robust onset of nuclear dynein–mediated centrosome separation. Third, we find that the initial position of centrosomes, between the male pronucleus and cell cortex at the embryo posterior, is a key determinant in organizing microtubule aster asymmetry to power nuclear dynein–dependent separation. Overall our work reveals that accurate initial centrosome position, together with steric interactions, ensures proper anisotropic organization of nuclear dynein forces to separate centrosomes, thus ensuring robust bipolar spindle assembly.
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spelling pubmed-56870192018-01-22 Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes De Simone, Alessandro Gönczy, Pierre Mol Biol Cell Brief Reports Centrosome separation along the surface of the nucleus at the onset of mitosis is critical for bipolar spindle assembly. Dynein anchored on the nuclear envelope is known to be important for centrosome separation, but it is unclear how nuclear dynein forces are organized in an anisotropic manner to promote the movement of centrosomes away from each other. Here we use computational simulations of Caenorhabditis elegans embryos to address this fundamental question, testing three potential mechanisms by which nuclear dynein may act. First, our analysis shows that expansion of the nuclear volume per se does not generate nuclear dynein–driven separation forces. Second, we find that steric interactions between microtubules and centrosomes contribute to robust onset of nuclear dynein–mediated centrosome separation. Third, we find that the initial position of centrosomes, between the male pronucleus and cell cortex at the embryo posterior, is a key determinant in organizing microtubule aster asymmetry to power nuclear dynein–dependent separation. Overall our work reveals that accurate initial centrosome position, together with steric interactions, ensures proper anisotropic organization of nuclear dynein forces to separate centrosomes, thus ensuring robust bipolar spindle assembly. The American Society for Cell Biology 2017-11-07 /pmc/articles/PMC5687019/ /pubmed/28701341 http://dx.doi.org/10.1091/mbc.E16-12-0823 Text en © 2017 De Simone and Gönczy. 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 Brief Reports
De Simone, Alessandro
Gönczy, Pierre
Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
title Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
title_full Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
title_fullStr Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
title_full_unstemmed Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
title_short Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
title_sort computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687019/
https://www.ncbi.nlm.nih.gov/pubmed/28701341
http://dx.doi.org/10.1091/mbc.E16-12-0823
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