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Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly

Mitotic spindle assembly is crucial for chromosome segregation and relies on bundles of microtubules that extend from the poles and overlap in the middle. However, how these structures form remains poorly understood. Here we show that overlap bundles arise through a network-to-bundles transition dri...

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Autores principales: Matković, Jurica, Ghosh, Subhadip, Ćosić, Mateja, Eibes, Susana, Barišić, Marin, Pavin, Nenad, Tolić, Iva M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701229/
https://www.ncbi.nlm.nih.gov/pubmed/36435852
http://dx.doi.org/10.1038/s41467-022-34957-4
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author Matković, Jurica
Ghosh, Subhadip
Ćosić, Mateja
Eibes, Susana
Barišić, Marin
Pavin, Nenad
Tolić, Iva M.
author_facet Matković, Jurica
Ghosh, Subhadip
Ćosić, Mateja
Eibes, Susana
Barišić, Marin
Pavin, Nenad
Tolić, Iva M.
author_sort Matković, Jurica
collection PubMed
description Mitotic spindle assembly is crucial for chromosome segregation and relies on bundles of microtubules that extend from the poles and overlap in the middle. However, how these structures form remains poorly understood. Here we show that overlap bundles arise through a network-to-bundles transition driven by kinetochores and chromosomes. STED super-resolution microscopy reveals that PRC1-crosslinked microtubules initially form loose arrays, which become rearranged into bundles. Kinetochores promote microtubule bundling by lateral binding via CENP-E/kinesin-7 in an Aurora B-regulated manner. Steric interactions between the bundle-associated chromosomes at the spindle midplane drive bundle separation and spindle widening. In agreement with experiments, theoretical modeling suggests that bundles arise through competing attractive and repulsive mechanisms. Finally, perturbation of overlap bundles leads to inefficient correction of erroneous kinetochore-microtubule attachments. Thus, kinetochores and chromosomes drive coarsening of a uniform microtubule array into overlap bundles, which promote not only spindle formation but also chromosome segregation fidelity.
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spelling pubmed-97012292022-11-28 Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly Matković, Jurica Ghosh, Subhadip Ćosić, Mateja Eibes, Susana Barišić, Marin Pavin, Nenad Tolić, Iva M. Nat Commun Article Mitotic spindle assembly is crucial for chromosome segregation and relies on bundles of microtubules that extend from the poles and overlap in the middle. However, how these structures form remains poorly understood. Here we show that overlap bundles arise through a network-to-bundles transition driven by kinetochores and chromosomes. STED super-resolution microscopy reveals that PRC1-crosslinked microtubules initially form loose arrays, which become rearranged into bundles. Kinetochores promote microtubule bundling by lateral binding via CENP-E/kinesin-7 in an Aurora B-regulated manner. Steric interactions between the bundle-associated chromosomes at the spindle midplane drive bundle separation and spindle widening. In agreement with experiments, theoretical modeling suggests that bundles arise through competing attractive and repulsive mechanisms. Finally, perturbation of overlap bundles leads to inefficient correction of erroneous kinetochore-microtubule attachments. Thus, kinetochores and chromosomes drive coarsening of a uniform microtubule array into overlap bundles, which promote not only spindle formation but also chromosome segregation fidelity. Nature Publishing Group UK 2022-11-27 /pmc/articles/PMC9701229/ /pubmed/36435852 http://dx.doi.org/10.1038/s41467-022-34957-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Matković, Jurica
Ghosh, Subhadip
Ćosić, Mateja
Eibes, Susana
Barišić, Marin
Pavin, Nenad
Tolić, Iva M.
Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
title Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
title_full Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
title_fullStr Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
title_full_unstemmed Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
title_short Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
title_sort kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701229/
https://www.ncbi.nlm.nih.gov/pubmed/36435852
http://dx.doi.org/10.1038/s41467-022-34957-4
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