Molecular mechanisms facilitating the initial kinetochore encounter with spindle microtubules

Author:

Vasileva Vanya1,Gierlinski Marek12ORCID,Yue Zuojun1,O’Reilly Nicola3ORCID,Kitamura Etsushi1ORCID,Tanaka Tomoyuki U.1ORCID

Affiliation:

1. Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK

2. Data Analysis Group, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK

3. Lincoln’s Inn Fields Laboratory, The Francis Crick Institute, London WC2A 3LY, England, UK

Abstract

The initial kinetochore (KT) encounter with a spindle microtubule (MT; KT capture) is one of the rate-limiting steps in establishing proper KT–MT interaction during mitosis. KT capture is facilitated by multiple factors, such as MT extension in various directions, KT diffusion, and MT pivoting. In addition, KTs generate short MTs, which subsequently interact with a spindle MT. KT-derived MTs may facilitate KT capture, but their contribution is elusive. In this study, we find that Stu1 recruits Stu2 to budding yeast KTs, which promotes MT generation there. By removing Stu2 specifically from KTs, we show that KT-derived MTs shorten the half-life of noncaptured KTs from 48–49 s to 28–34 s. Using computational simulation, we found that multiple factors facilitate KT capture redundantly or synergistically. In particular, KT-derived MTs 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 KT encounter with spindle MTs.

Funder

Wellcome Trust

European Research Council

Human Frontier Science Program

Medical Research Council

Publisher

Rockefeller University Press

Subject

Cell Biology

Reference56 articles.

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