Molecular mechanisms facilitating the initial kinetochore encounter with spindle microtubules

Vanya Vasileva, Marek Gierlinski, Zuojun Yue, Nicola O'Reilly, Etsushi Kitamura, Tomoyuki U. Tanaka (Lead / Corresponding author)

Research output: Contribution to journalArticle

6 Citations (Scopus)
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Abstract

The initial kinetochore encounter with a spindle microtubule (kinetochore capture) is one of the rate-limiting steps in establishing proper kinetochore–microtubule interaction during mitosis. Kinetochore capture is facilitated by multiple factors such as microtubule extension in various directions, kinetochore diffusion and microtubule pivoting. In addition, kinetochores generate short microtubules, which subsequently interact with a spindle microtubule. Kinetochore-derived microtubules may facilitate kinetochore capture, but their contribution is elusive. Here we find that Stu1 recruits Stu2 to budding yeast kinetochores, which promotes microtubule generation there. By removing Stu2 specifically from kinetochores, we show that kinetochore-derived microtubules shorten the half-life of non-captured kinetochores from 48–49 to 28–34 seconds. Using computational simulation we find that multiple factors facilitate kinetochore capture, redundantly or synergistically. In particular, kinetochore-derived microtubules play important roles both by making a significant contribution on their own and by synergistically enhancing the effects of KT diffusion and MT pivoting. Our study reveals fundamental mechanisms facilitating the initial kinetochore encounter with spindle microtubules.
Original languageEnglish
Pages (from-to)1809-1822
Number of pages14
JournalJournal of Cell Biology
Volume216
Issue number6
Early online date26 Apr 2017
DOIs
Publication statusPublished - 26 Apr 2017

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Kinetochores
Microtubules
Saccharomycetales
Mitosis

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@article{09e561a0474c44e5b46126af28272bda,
title = "Molecular mechanisms facilitating the initial kinetochore encounter with spindle microtubules",
abstract = "The initial kinetochore encounter with a spindle microtubule (kinetochore capture) is one of the rate-limiting steps in establishing proper kinetochore–microtubule interaction during mitosis. Kinetochore capture is facilitated by multiple factors such as microtubule extension in various directions, kinetochore diffusion and microtubule pivoting. In addition, kinetochores generate short microtubules, which subsequently interact with a spindle microtubule. Kinetochore-derived microtubules may facilitate kinetochore capture, but their contribution is elusive. Here we find that Stu1 recruits Stu2 to budding yeast kinetochores, which promotes microtubule generation there. By removing Stu2 specifically from kinetochores, we show that kinetochore-derived microtubules shorten the half-life of non-captured kinetochores from 48–49 to 28–34 seconds. Using computational simulation we find that multiple factors facilitate kinetochore capture, redundantly or synergistically. In particular, kinetochore-derived microtubules play important roles both by making a significant contribution on their own and by synergistically enhancing the effects of KT diffusion and MT pivoting. Our study reveals fundamental mechanisms facilitating the initial kinetochore encounter with spindle microtubules.",
author = "Vanya Vasileva and Marek Gierlinski and Zuojun Yue and Nicola O'Reilly and Etsushi Kitamura and Tanaka, {Tomoyuki U.}",
note = "This work was supported by the Wellcome Trust (096535, 083524, 097945), an ERC advanced grant (322682), Human Frontier Science Program (RGP0035/2009) and the Medical Research Council (K015869) and. T.U.T. is a Wellcome Trust Principal Research Fellow.",
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Molecular mechanisms facilitating the initial kinetochore encounter with spindle microtubules. / Vasileva, Vanya; Gierlinski, Marek; Yue, Zuojun; O'Reilly, Nicola; Kitamura, Etsushi; Tanaka, Tomoyuki U. (Lead / Corresponding author).

In: Journal of Cell Biology, Vol. 216, No. 6, 26.04.2017, p. 1809-1822.

Research output: Contribution to journalArticle

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T1 - Molecular mechanisms facilitating the initial kinetochore encounter with spindle microtubules

AU - Vasileva, Vanya

AU - Gierlinski, Marek

AU - Yue, Zuojun

AU - O'Reilly, Nicola

AU - Kitamura, Etsushi

AU - Tanaka, Tomoyuki U.

N1 - This work was supported by the Wellcome Trust (096535, 083524, 097945), an ERC advanced grant (322682), Human Frontier Science Program (RGP0035/2009) and the Medical Research Council (K015869) and. T.U.T. is a Wellcome Trust Principal Research Fellow.

PY - 2017/4/26

Y1 - 2017/4/26

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