Centrosomal Aki1 and cohesin function in separase-regulated centriole disengagement
Centrosomal Aki1 and cohesin function in separase-regulated centriole disengagement
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DOI：
10.1083/jcb.200906019
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发表时间：
2009-11-30
影响因子：
7.8
通讯作者：
Fujita, Naoya
中科院分区：
文献类型：
--
作者：
Nakamura, Akito;Arai, Hiroyuki;Fujita, Naoya
分裂后期的姐妹染色单体分离是由分离酶介导的粘连蛋白亚基Scc1的切割触发的。中心粒分离也需要分离酶。分离酶的这种双重作用允许同时控制这些事件，以实现准确的中期到后期的过渡。虽然姐妹染色单体凝聚的分子机制已被阐明，中心粒凝聚的了解甚少。在这项研究中，我们表明，Akt激酶相互作用蛋白1（Aki1）定位于中心体和调节中心粒凝聚力。Aki1缺失导致多极纺锤体的形成，伴随着中心粒分裂，这是分离酶依赖的。我们还表明，粘附素亚基定位于中心体和中心体Scc1裂解分离酶巧合与染色质Scc1，这表明Scc1作为连接器的中心粒以及姐妹染色单体的作用。有趣的是，Scc1缺失强烈诱导中心粒分裂。此外，Aki1与中心体中的粘着蛋白相互作用，这种相互作用是中心粒凝聚所必需的。我们证明，中心体相关Aki1和cohesin发挥关键作用，防止过早分裂的中心粒凝聚力。
Sister chromatid separation at anaphase is triggered by cleavage of the cohesin subunit Scc1, which is mediated by separase. Centriole disengagement also requires separase. This dual role of separase permits concurrent control of these events for accurate metaphase to anaphase transition. Although the molecular mechanism underlying sister chromatid cohesion has been clarified, that of centriole cohesion is poorly understood. In this study, we show that Akt kinase-interacting protein 1 (Aki1) localizes to centrosomes and regulates centriole cohesion. Aki1 depletion causes formation of multipolar spindles accompanied by centriole splitting, which is separase dependent. We also show that cohesin subunits localize to centrosomes and that centrosomal Scc1 is cleaved by separase coincidentally with chromatin Scc1, suggesting a role of Scc1 as a connector of centrioles as well as sister chromatids. Interestingly, Scc1 depletion strongly induces centriole splitting. Furthermore, Aki1 interacts with cohesin in centrosomes, and this interaction is required for centriole cohesion. We demonstrate that centrosome-associated Aki1 and cohesin play pivotal roles in preventing premature cleavage in centriole cohesion.