Metaphase kinetochore movements are regulated by kinesin-8 motors and microtubule dynamic instability

Klemm, Anna H. and Bosilj, Agneza and Glunčić, Matko and Pavin, Nenad and Tolić, Iva Marija (2018) Metaphase kinetochore movements are regulated by kinesin-8 motors and microtubule dynamic instability. Molecular Biology of the Cell, 29. pp. 1332-1345. ISSN 1059-1524

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Abstract

During metaphase, sister chromatids are connected to microtubules extending from the opposite spindle poles via kinetochores, protein complexes on the chromosome. Kinetochores congress to the equatorial plane of the spindle and oscillate around it, with kinesin-8 motors restricting these movements. Yet, the physical mechanism underlying kinetochore movements is unclear. We show that kinetochore movements in the fission yeast Schizosaccharomyces pombe are regulated by kinesin-8-promoted microtubule catastrophe, force-induced rescue and microtubule dynamic instability. A candidate screen showed that among the selected motors only kinesin-8 motors Klp5/Klp6 are required for kinetochore centering. Kinesin-8 accumulates at the end of microtubules, where it promotes catastrophe. Laser ablation of the spindle resulted in kinetochore movement towards the intact spindle pole in wild-type and klp5Δ cells, suggesting that kinetochore movement is driven by pulling forces. Our theoretical model with Langevin description of microtubule dynamic instability shows that kinesin-8 motors are required for kinetochore centering, whereas sensitivity of rescue to force is necessary for the generation of oscillations. We found that irregular kinetochore movements occur for a broader range of parameters than regular oscillations. Thus, our work provides an explanation for how regulation of microtubule dynamic instability contributes to kinetochore congression and the accompanying movements around the spindle center.

Item Type: Article
Keywords: mitotic spindle, kinetochore microtubules, kinesin-8 motors, microtubule dynamic instability, kinetochore oscillations, metaphase model
Date: 2018
Subjects: NATURAL SCIENCES > Biology
NATURAL SCIENCES > Interdisciplinary Natural Sciences
NATURAL SCIENCES > Physics
Additional Information: © 2018 Klemm, Bosilj, et al. 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). Submitted: 28 November 2017. Revised: 27 March 2018. Accepted: 29 March 2018.
Divisions: Faculty of Science > Department of Physics
Publisher: American Society for Cell Biology
Depositing User: Gordana Stubičan Ladešić
Date Deposited: 07 Mar 2019 13:23
Last Modified: 07 Mar 2019 13:23
URI: http://digre.pmf.unizg.hr/id/eprint/5881

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