Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis.

Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis.
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DOI:
10.1098/rsob.160248
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发表时间:
2016-10
期刊:
影响因子:
5.8
通讯作者:
D'Avino PP
D'Avino PP
中科院分区:
生物学2区
文献类型:
--
作者:
Capalbo L;Mela I;Abad MA;Jeyaprakash AA;Edwardson JM;D'Avino PP

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染色体乘客复合物(CPC)-由极光B激酶,Borealin,Survivin和INCENP组成-调查整个细胞分裂过程中基因组分离的保真度。已提出CPC通过调控ESCRT-III CHMP 4C组分控制两个子细胞的最终分离(称为分离)来防止多倍体。然而,分子细节仍然不清楚。使用原子力显微镜,我们表明,CHMP 4C结合和重塑膜在体外。Borealin阻止CHMP 4C与膜的结合,而Aurora B干扰CHMP 4C的膜重塑活性。此外,我们表明,CHMP 4C磷酸化是不需要其组装成螺旋丝在purisis网站和两个明显的本地化池的磷酸化CHMP 4C胞质分裂过程中存在。我们还描述了CHMP 4C在末期细胞中的相互作用组,并表明centralspindlin复合物在胞质分裂中优先与未磷酸化的CHMP 4C相关联。我们的研究结果表明,CHMP 4C的逐渐去磷酸化触发了CPC和centralspindlin之间的“中继”机制,该机制调节CHMP 4C的及时分布和激活以执行任务。
The chromosomal passenger complex (CPC)—composed of Aurora B kinase, Borealin, Survivin and INCENP—surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro. Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a ‘relay’ mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.
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