Chromokinesins: localization-dependent functions and regulation during cell division.

Chromokinesins: localization-dependent functions and regulation during cell division.
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DOI:
10.1042/bst0391154
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发表时间:
2011-10
影响因子:
3.9
通讯作者:
D. Vanneste;Vanessa Ferreira;I. Vernos
D. Vanneste;Vanessa Ferreira;I. Vernos
中科院分区:
生物学3区
文献类型:
--
作者:
D. Vanneste;Vanessa Ferreira;I. Vernos

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双极纺锤体是一种高度动态的结构,其在染色体周围瞬时组装并提供染色体分离所需的机械支撑和力。纺锤体组装和染色体运动依赖于微管动力学的调节和各种分子马达施加的力的精细平衡。染色体本身就是纺锤体组装的核心参与者。它们产生RanGTP梯度,触发微管成核和局部稳定,并且它们通过靶向染色质的马达与微管动态相互作用。我们以前已经确定并表征了这些所谓的chromokinesins中的两个:Xkid(驱动蛋白10)和Xklp 1(驱动蛋白4)。最近,我们发现Hklp 2/kif 15(驱动蛋白12)通过与人类细胞中的Ki-67相互作用靶向染色体,因此是一种新的染色体驱动蛋白。Hklp 2还以TPX 2(Xklp 2的靶向蛋白)依赖性方式在有丝分裂期间特异性地与微管结合。我们已经表明,Hklp 2参与纺锤体极分离和维持纺锤体双极性中期。为了更好地理解Hklp 2的功能,我们进行了详细的域分析。有趣的是,从其在染色体臂上的定位来看,Hklp 2似乎限制了纺锤体极分离。在本综述中,我们总结了目前的知识与染色体臂在细胞分裂过程中,包括Hklp 2作为一个新的成员,这个所谓的chromokinesin家族的不同驱动蛋白的功能和调节。
The bipolar spindle is a highly dynamic structure that assembles transiently around the chromosomes and provides the mechanical support and the forces required for chromosome segregation. Spindle assembly and chromosome movements rely on the regulation of microtubule dynamics and a fine balance of forces exerted by various molecular motors. Chromosomes are themselves central players in spindle assembly. They generate a RanGTP gradient that triggers microtubule nucleation and stabilization locally and they interact dynamically with the microtubules through motors targeted to the chromatin. We have previously identified and characterized two of these so-called chromokinesins: Xkid (kinesin 10) and Xklp1 (kinesin 4). More recently, we found that Hklp2/kif15 (kinesin 12) is targeted to the chromosomes through an interaction with Ki-67 in human cells and is therefore a novel chromokinesin. Hklp2 also associates with the microtubules specifically during mitosis, in a TPX2 (targeting protein for Xklp2)-dependent manner. We have shown that Hklp2 participates in spindle pole separation and in the maintenance of spindle bipolarity in metaphase. To better understand the function of Hklp2, we have performed a detailed domain analysis. Interestingly, from its positioning on the chromosome arms, Hklp2 seems to restrict spindle pole separation. In the present review, we summarize the current knowledge of the function and regulation of the different kinesins associated with chromosome arms during cell division, including Hklp2 as a novel member of this so-called chromokinesin family.