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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. (2022) Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly. Nature Communications, 13 (1). ISSN 2041-1723

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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.

Item Type: Article
Uncontrolled Keywords: overlap bundles, mitotic spindle, CENP-E, Aurora B, mitosis, motor proteins
Subjects: NATURAL SCIENCES > Biology
NATURAL SCIENCES > Interdisciplinary Natural Sciences
Divisions: Division of Molecular Biology
Project titleProject leaderProject codeProject type
Mehanizmi nastajanja snopova mikrotubula potrebni za sazrijevanje diobenog vretenaTolić, IvaPZS-2019-02-7653HRZZ
Molekularno podrijetlo aneuploidija u zdravim i bolesnim ljudskim tkivimaTolić, Iva; Pavin, Nenad855158EK
Inovativni protokoli mikroskopije za interdisciplinarna istraživanja u biomediciniTolić, Iva MarijaKK.
Depositing User: Iva Tolić
Date Deposited: 03 Apr 2023 09:06
DOI: 10.1038/s41467-022-34957-4

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