CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis
CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis
复制标题
CENP-E 驱动蛋白与 SKAP 蛋白相互作用以协调有丝分裂中准确的染色体分离
DOI：
10.1074/jbc.m111.277194
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发表时间：
2012-01-06
影响因子：
4.8
通讯作者：
Yao, Xuebiao
中科院分区：
文献类型：
--
作者：
Huang, Yuejia;Wang, Wenwen;Yao, Xuebiao
有丝分裂染色体分离是由纺锤体微管与动粒的动态相互作用所协调的。尽管先前的研究表明有丝分裂驱动蛋白CENP-E在纺锤体微管与动粒的连接和有丝分裂检查点信号级联之间形成了联系，但哺乳动物细胞中动态动粒-微管相互作用的分子机制仍然难以捉摸。在这里，我们确定了CENP-E和SKAP之间的一种新型相互作用，该相互作用在控制动态运动舞蹈-微管相互作用方面发挥协同作用。SKAP在体外与CENP-E的C-末端尾部结合，并且对于体内精确的着丝粒-微管附着是必需的。免疫电镜分析表明，SKAP是哺乳动物着丝粒动粒冠纤维的组成部分。通过RNA干扰耗尽SKAP或CENP-E导致动粒间张力的显著降低，这导致染色体错误分离，延长了实现中期对齐的延迟。重要的是，SKAP在体外与微管结合，这种相互作用被CENP-E协同。基于这些发现，我们建议SKAP与CENP-E合作，以协调动态kinetochore-microtubule相互作用，实现忠实的染色体分离。
Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.