Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and kinesin-8.
Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and kinesin-8.
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DOI：
10.1083/jcb.201006028
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发表时间：
2010-11-15
期刊：
影响因子：
--
通讯作者：
Barnes G
中科院分区：
文献类型：
--
作者：
Woodruff JB;Drubin DG;Barnes G
对芽殖酵母中纺锤体解体的大规模分析确定了纺锤体半体分离、纺锤体伸长停滞以及极间微管解聚所需的因子。
有丝分裂纺锤体是一种复杂且动态的结构。尽管对于纺锤体如何组装以及介导染色体分离已经有了很多了解，但在末期纺锤体如何快速且不可逆地解体则不太清楚。我们在芽殖酵母中使用合成致死筛选来鉴定纺锤体解体有缺陷的突变体。对在此过程中有缺陷的9个突变体进行了纺锤体解体的实时活细胞成像分析。该分析结果表明，纺锤体解体是通过机制不同但功能上有重叠的子过程实现的：纺锤体半体分离、纺锤体伸长停滞以及极间微管解聚的起始。这些子过程在很大程度上受后期促进复合物、极光B激酶和驱动蛋白 - 8的调控。对这些子过程的组合抑制产生了具有超稳定纺锤体残余物且细胞周期进程有严重缺陷的细胞，这表明快速的纺锤体解体对于细胞增殖至关重要。
A large-scale analysis of spindle disassembly in budding yeast identifies factors required for disengagement of spindle halves, arrest of spindle elongation, and depolymerization of interpolar microtubules. The mitotic spindle is a complex and dynamic structure. Although much has been learned about how spindles assemble and mediate chromosome segregation, how spindles rapidly and irreversibly disassemble during telophase is less clear. We used synthetic lethal screens in budding yeast to identify mutants defective in spindle disassembly. Real-time, live cell imaging analysis of spindle disassembly was performed on nine mutants defective in this process. Results of this analysis suggest that spindle disassembly is achieved by mechanistically distinct but functionally overlapping subprocesses: disengagement of the spindle halves, arrest of spindle elongation, and initiation of interpolar microtubule depolymerization. These subprocesses are largely governed by the anaphase-promoting complex, Aurora B kinase, and kinesin-8. Combinatorial inhibition of these subprocesses yielded cells with hyperstable spindle remnants and dramatic defects in cell cycle progression, establishing that rapid spindle disassembly is crucial for cell proliferation.
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