Vasileva Vanya, Gierlinski Marek, Yue Zuojun, O'Reilly Nicola, Kitamura Etsushi, Tanaka Tomoyuki U
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Data Analysis Group, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
J Cell Biol. 2017 Jun 5;216(6):1609-1622. doi: 10.1083/jcb.201608122. Epub 2017 Apr 26.
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.
动粒(KT)与纺锤体微管(MT;KT捕获)的初次接触是有丝分裂期间建立正确的KT-MT相互作用的限速步骤之一。多种因素促进KT捕获,如MT向各个方向延伸、KT扩散和MT旋转。此外,动粒产生短微管,这些短微管随后与纺锤体微管相互作用。动粒衍生的微管可能促进KT捕获,但其作用尚不清楚。在本研究中,我们发现Stu1将Stu2招募到出芽酵母的动粒上,从而促进那里的微管生成。通过特异性地从动粒中去除Stu2,我们发现动粒衍生的微管将未捕获动粒的半衰期从48 - 49秒缩短至28 - 34秒。通过计算模拟,我们发现多种因素以冗余或协同的方式促进KT捕获。特别是,动粒衍生的微管自身做出重大贡献,并通过协同增强KT扩散和MT旋转的作用发挥重要作用。我们的研究揭示了促进动粒与纺锤体微管初次接触的基本机制。