Kif18A and Chromokinesins Confine Centromere Movements via Microtubule Growth Suppression and Spatial Control of Kinetochore Tension

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• 作者：Jason Stumpff¹ ; ² ; ^{jstumpff@uvm.edu} ; Michael Wagenbach¹ ; Andrew Franck¹ ; Charles  ; L. Asbury¹ ; Linda Wordeman¹ ; ^{worde@washington.edu}
• 刊名：Developmental Cell
• 出版年：2012
• 期刊代码：10_15345807
• 类别：bio
• 出版时间：15 May, 2012
• 卷：22
• 期：5
• 页码：1017-1029
• 文件大小：1532 K

摘要

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Summary

Alignment of chromosomes at the metaphase plate is a signature of cell division in metazoan cells, yet the mechanisms controlling this process remain ambiguous. Here we use a combination of quantitative live-cell imaging and reconstituted dynamic microtubule assays to investigate the molecular control of mitotic centromere movements. We establish that Kif18A (kinesin-8) attenuates centromere movement by directly promoting microtubule pausing in a concentration-dependent manner. This activity provides the dominant mechanism for restricting centromere movement to the spindle midzone. Furthermore, polar ejection forces spatially confine chromosomes via position-dependent regulation of kinetochore tension and centromere switch rates. We demonstrate that polar ejection forces are antagonistically modulated by chromokinesins. These pushing forces depend on Kid (kinesin-10) activity and are antagonized by Kif4A (kinesin-4), which functions to directly suppress microtubule growth. These data support a model in which Kif18A and polar ejection forces synergistically promote centromere alignment via spatial control of kinetochore-microtubule dynamics.

Video Abstract

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