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有丝分裂驱动蛋白-5 Cin8在酵母有丝分裂中的双向运动性和马达聚集的潜在生理作用。

A potential physiological role for bi-directional motility and motor clustering of mitotic kinesin-5 Cin8 in yeast mitosis.

作者信息

Shapira Ofer, Goldstein Alina, Al-Bassam Jawdat, Gheber Larisa

机构信息

Department of Chemistry and the Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.

Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA

出版信息

J Cell Sci. 2017 Feb 15;130(4):725-734. doi: 10.1242/jcs.195040. Epub 2017 Jan 9.

DOI:10.1242/jcs.195040
PMID:28069834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5339886/
Abstract

The bipolar kinesin-5 Cin8 switches from minus- to plus-end-directed motility under various conditions The mechanism and physiological significance of this switch remain unknown. Here, we show that under high ionic strength conditions, Cin8 moves towards and concentrates in clusters at the minus ends of stable and dynamic microtubules. Clustering of Cin8 induces a switch from fast minus- to slow plus-end-directed motility and forms sites that capture antiparallel microtubules (MTs) and induces their sliding apart through plus-end-directed motility. In early mitotic cells with monopolar spindles, Cin8 localizes near the spindle poles at microtubule minus ends. This localization is dependent on the minus-end-directed motility of Cin8. In cells with assembled bipolar spindles, Cin8 is distributed along the spindle microtubules. We propose that minus-end-directed motility is required for Cin8 clustering near the spindle poles before spindle assembly. Cin8 clusters promote the capture of microtubules emanating from the neighboring spindle poles and mediate their antiparallel sliding. This activity is essential to maximize microtubule crosslinking before bipolar spindle assembly and to induce the initial separation of the spindle poles.

摘要

双极驱动蛋白-5 Cin8在各种条件下从向负端运动转变为向正端运动。这种转变的机制和生理意义尚不清楚。在这里,我们表明,在高离子强度条件下,Cin8向稳定和动态微管的负端移动并聚集在这些负端的簇中。Cin8的聚集诱导了从快速向负端运动到缓慢向正端运动的转变,并形成捕获反平行微管(MTs)的位点,并通过向正端运动诱导它们分开滑动。在具有单极纺锤体的早期有丝分裂细胞中,Cin8定位于纺锤体极附近微管的负端。这种定位依赖于Cin8的向负端运动。在具有组装好的双极纺锤体的细胞中,Cin8沿着纺锤体微管分布。我们提出,在纺锤体组装之前,向负端运动是Cin8在纺锤体极附近聚集所必需的。Cin8簇促进捕获从相邻纺锤体极发出的微管并介导它们的反平行滑动。这种活动对于在双极纺锤体组装之前最大化微管交联以及诱导纺锤体极的初始分离至关重要。

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本文引用的文献

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Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7483-E7489. doi: 10.1073/pnas.1611581113. Epub 2016 Nov 9.
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Motile properties of the bi-directional kinesin-5 Cin8 are affected by phosphorylation in its motor domain.双向驱动蛋白-5 Cin8 的运动特性受其马达结构域磷酸化的影响。
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Kinesin-5 is a microtubule polymerase.驱动蛋白-5是一种微管聚合酶。
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A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes.一种三步的微管组织中心(MTOC)碎片化机制有助于小鼠卵母细胞中的双极纺锤体组装。
Nat Commun. 2015 Jul 6;6:7217. doi: 10.1038/ncomms8217.
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Mitotic slippage and expression of survivin are linked to differential sensitivity of human cancer cell-lines to the Kinesin-5 inhibitor monastrol.有丝分裂滑移和survivin的表达与人类癌细胞系对驱动蛋白-5抑制剂monastrol的不同敏感性相关。
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J Biol Chem. 2015 Jul 3;290(27):16841-50. doi: 10.1074/jbc.M114.620799. Epub 2015 May 19.
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Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers.有丝分裂动力蛋白驱动蛋白-5组装成双极四聚体的结构基础。
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Reconstituting dynamic microtubule polymerization regulation by TOG domain proteins.通过TOG结构域蛋白重建动态微管聚合调控
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Bidirectional motility of the fission yeast kinesin-5, Cut7.裂殖酵母驱动蛋白-5,Cut7 的双向运动。
Biochem Biophys Res Commun. 2014 Mar 28;446(1):231-4. doi: 10.1016/j.bbrc.2014.02.106. Epub 2014 Feb 28.
10
Kinesin-5 Kip1 is a bi-directional motor that stabilizes microtubules and tracks their plus-ends in vivo.驱动蛋白-5 Kip1是一种双向马达蛋白,可在体内稳定微管并追踪其正端。
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