GTSE1 regulates spindle microtubule dynamics to control Aurora B kinase and Kif4A chromokinesin on chromosome arms.

GTSE1 regulates spindle microtubule dynamics to control Aurora B kinase and Kif4A chromokinesin on chromosome arms.
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DOI:
10.1083/jcb.201610012
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发表时间:
2017-10-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Gorbsky GJ
Gorbsky GJ
中科院分区:
其他
文献类型:
--
作者:
Tipton AR;Wren JD;Daum JR;Siefert JC;Gorbsky GJ

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有丝分裂涉及多个途径的复杂相互作用,其中一些尚未被表征。Tipton等人使用生物信息学来暗示GTSE 1参与有丝分裂。GTSE 1的缺失破坏了染色体排列和纺锤体极的完整性,部分原因是纺锤体微管的超稳定性和染色体臂上Aurora B激酶和Kif4A色动蛋白的缺失。在有丝分裂中,微管的动态组装和拆卸对于正常的染色体运动和分离至关重要。微管周转率在不同的有丝分裂纺锤体微管之间变化,取决于它们在纺锤体内的空间分布。不同种类的纺锤体微管之间的周转是如何受到差异调节的,以及由此产生的差异周转对染色体运动的意义仍然是一个谜。作为一种新的策略,我们使用全球微阵列荟萃分析(GAMMA),一种生物信息学方法,以确定新的有丝分裂调节剂,在这项研究中,我们描述了G2和S期表达蛋白1(GTSE1)。GTSE 1仅在G2和M期晚期表达。从核膜破裂到后期开始,GTSE1优先结合最稳定的有丝分裂纺锤体微管并促进其周转。耗尽GTSE 1的细胞显示在中期板的染色体排列和纺锤体极完整性方面的缺陷。这些缺陷伴随着稳定的有丝分裂纺锤体微管比例的增加。这种微管周转减少的结果是染色体臂上极光B激酶的募集和活性减少。Aurora B的这种减少导致染色体驱动蛋白Kif4A与染色体臂的结合减少。
Mitosis involves complex interactions of multiple pathways, some yet uncharacterized. Tipton et al. use bioinformatics to implicate GTSE1 in mitosis. Depletion of GTSE1 disrupts chromosome alignment and spindle pole integrity, in part because of hyperstabilization of spindle microtubules and depletion of Aurora B kinase and Kif4A chromokinesin on chromosome arms. In mitosis, the dynamic assembly and disassembly of microtubules are critical for normal chromosome movement and segregation. Microtubule turnover varies among different mitotic spindle microtubules, dictated by their spatial distribution within the spindle. How turnover among the various classes of spindle microtubules is differentially regulated and the resulting significance of differential turnover for chromosome movement remains a mystery. As a new tactic, we used global microarray meta-analysis (GAMMA), a bioinformatic method, to identify novel regulators of mitosis, and in this study, we describe G2- and S phase–expressed protein 1 (GTSE1). GTSE1 is expressed exclusively in late G2 and M phase. From nuclear envelope breakdown until anaphase onset, GTSE1 binds preferentially to the most stable mitotic spindle microtubules and promotes their turnover. Cells depleted of GTSE1 show defects in chromosome alignment at the metaphase plate and in spindle pole integrity. These defects are coupled with an increase in the proportion of stable mitotic spindle microtubules. A consequence of this reduced microtubule turnover is diminished recruitment and activity of Aurora B kinase on chromosome arms. This decrease in Aurora B results in diminished binding of the chromokinesin Kif4A to chromosome arms.
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