The Role of Hklp2 in the Stabilization and Maintenance of Spindle Bipolarity
The Role of Hklp2 in the Stabilization and Maintenance of Spindle Bipolarity
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DOI：
10.1016/j.cub.2009.09.019
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发表时间：
2009-11-03
期刊：
影响因子：
9.2
通讯作者：
Vernos, Isabelle
中科院分区：
文献类型：
--
作者：
Vanneste, David;Takagi, Masatoshi;Vernos, Isabelle
主轴双极性依赖于各种分子马达施加的力的精细平衡[1-4]。在大多数动物细胞中，纺锤体双极性需要持续向外的力来推动纺锤体极点分开，这种活动是由Eg5提供的，Eg5是一种保守的同四聚体+端向驱动蛋白，它交联并使反平行的微管分开。这些推力被向内的负方向力所平衡。损害Eg5和动力蛋白可以恢复功能双极纺锤体[4]的形成，尽管其机制尚不清楚。目前的模型也无法解释为什么在某些系统中，抑制Eg5不会促进双极纺锤体崩溃[6,7]，或者为什么增加Eg5水平不会干扰双极纺锤体组装(8)。此外，秀丽隐杆线虫的Eg5同源不需要双极纺锤体形成[9]。我们发现HkIp2蛋白参与了双极纺锤体的组装和稳定。HkIp2以依赖tpx2的方式定位于有丝分裂微管，并通过Ki67定位于染色体。我们的数据表明，它的作用机制与Eg5明显不同，并与之互补，为驱动双极主轴形成和维持的机制提供了额外的理解。
Spindle bipolarity relies on a fine balance of forces exerted by various molecular motors [1-4]. In most animal cells, spindle bipolarity requires sustained outward forces to push the spindle poles apart, an activity that is provided by Eg5, a conserved homotetrameric plus-end-directed kinesin that crosslinks and slides antiparallel microtubules apart [5]. These pushing forces are balanced by inward minus-end-directed forces. Impairing both Eg5 and dynein restores the formation of functional bipolar spindles [4], although the mechanism at play is far from clear. The current model also fails to explain why in some systems Eg5 inhibition does not promote bipolar spindle collapse [6, 7] or why increasing Eg5 levels does not interfere with bipolar spindle assembly (8]. Moreover, the C. elegans Eg5 ortholog is not required for bipolar spindle formation [9]. We show here that the kinesin HkIp2 participates in the assembly and stabilization of the bipolar spindle. HkIp2 localizes to the mitotic microtubules in a TPX2-dependent manner and to the chromosomes through Ki67. Our data indicate that its mechanism of action is clearly distinct from and complementary to that of Eg5, providing an additional understanding of the mechanism driving the formation and maintenance of the bipolar spindle.