The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly

The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly
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DOI:
10.1016/j.cell.2004.06.026
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发表时间:
2004-07-23
期刊:
影响因子:
64.5
通讯作者:
Funabiki, H
Funabiki, H
中科院分区:
生物学1区
文献类型:
--
作者:
Sampath, SC;Ohi, R;Funabiki, H

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在缺乏中心体的细胞中,例如在女性减数分裂中发现的细胞,染色体必须成核并稳定微管以形成双极纺锤体。在这里,我们报道了Dasra A和Dasra B的鉴定,这是脊椎动物染色体客运复合物的两个新成分,含有Incenp, Survivin和激酶Aurora B,并证明该复合物是染色质诱导的微管稳定和纺锤体形成所必需的。由于染色体乘客复合物耗损导致的微管稳定失败可以通过微管解聚激酶MCAK的共耗损来修复,MCAK的活性受到Aurora b的负调控。相反,我们发现染色质诱导的微管成核的RanGTP途径不需要染色体乘客复合物,这表明这两种途径的微管组装机制是不同的。我们认为,染色体客运复合体通过稳定染色质相关微管调节局部MCAK活性,从而允许纺锤体形成。
In cells lacking centrosomes, such as those found in female meiosis, chromosomes must nucleate and stabilize microtubules in order to form a bipolar spindle. Here we report the identification of Dasra A and Dasra B, two new components of the vertebrate chromosomal passenger complex containing Incenp, Survivin, and the kinase Aurora B, and demonstrate that this complex is required for chromatin-induced microtubule stabilization and spindle formation. The failure of microtubule stabilization caused by depletion of the chromosomal passenger complex was rescued by codepletion of the microtubule-depolymerizing kinesin MCAK, whose activity is negatively regulated by Aurora B. By contrast, we present evidence that the RanGTP pathway of chromatin-induced microtubule nucleation does not require the chromosomal passenger complex, indicating that the mechanisms of microtubule assembly by these two pathways are distinct. We propose that the chromosomal passenger complex regulates local MCAK activity to permit spindle formation via stabilization of chromatin-associated microtubules.