Kif15 Cooperates with Eg5 to Promote Bipolar Spindle Assembly
Kif15 Cooperates with Eg5 to Promote Bipolar Spindle Assembly
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DOI：
10.1016/j.cub.2009.08.027
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发表时间：
2009-11-03
期刊：
影响因子：
9.2
通讯作者：
Medema, Rene H.
中科院分区：
文献类型：
--
作者：
Tanenbaum, Marvin E.;Macurek, Libor;Medema, Rene H.
背景：双极纺锤体的形成是细胞分裂的重要步骤。双极纺锤体组装是由高度保守的微管马达Eg 5（驱动蛋白-5）驱动的，该马达可以使反平行的微管滑动分开以驱动中心体分离。然而，目前还不清楚是否以及如何额外的电机可以有助于中心体分离和双极spindle formation.Results：我们已经开发出一种新的检测方法，以确定电机参与纺锤体双极性，通过这种检测，我们确定Kif 15/Hklp 2（驱动蛋白-12，以下简称Kif 15）。Kif 15是不需要的纺锤体双极性在细胞与全部Eg 5活性，但成为必不可少的Eg 5时，部分抑制。我们发现Kif 15的主要功能是促进纺锤体的伸长，并确保纺锤体双极性的维持。尽管如此，异位表达Kif 15可以完全重建双极纺锤体组装在Eg 5活性的情况下，表明Kif 15可以取代所有必要的功能Eg 5在双极纺锤体组装。重要的是，这种活动的Kif 15依赖于它的相互作用与微管相关蛋白TPX 2，表明Kif 15-TPX 2复合物促进中心体separation.Conclusions：这些研究结果表明，类似于Eg 5，Kif 15可以驱动中心体分离在双极纺锤体组装。对于这种活动，Kif 15需要其运动域和其与TPX 2的相互作用。基于这些数据，我们提出Kif 15和TPX 2的复合物可以交联并将两个反平行的微管分开，从而驱动中心体分离。
Background: The formation of a bipolar spindle is an essential step during cell division. Bipolar spindle assembly is driven by the highly conserved microtubule motor Eg5 (kinesin-5), which can slide antiparallel microtubules apart to drive centrosome separation. However, it is currently unclear whether and how additional motors can contribute to centrosome separation and bipolar spindle formation.Results: We have developed a novel assay to identify motors involved in spindle bipolarity; via this assay, we identify Kif15/Hklp2 (kinesin-12, hereafter referred to as Kif15). Kif15 is not required for spindle bipolarity in cells with full Eg5 activity but becomes essential when Eg5 is partially inhibited. We show that the primary function of Kif15 is to promote spindle elongation and to ensure maintenance of spindle bipolarity. Nonetheless, ectopic expression of Kif15 can fully reconstitute bipolar spindle assembly in the absence of Eg5 activity, demonstrating that Kif15 can replace all essential functions of Eg5 in bipolar spindle assembly. Importantly, this activity of Kif15 depends on its interaction with the microtubule-associated protein TPX2, indicating that a Kif15-TPX2 complex promotes centrosome separation.Conclusions: These findings show that, similar to Eg5, Kif15 can drive centrosome separation during bipolar spindle assembly. For this activity, Kif15 requires both its motor domain and its interaction with TPX2. Based on these data, we propose that a complex of Kif15 and TPX2 can crosslink and slide two antiparallel microtubules apart, thereby driving centrosome separation.