Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation.
Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation.
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DOI：
10.1083/jcb.201105074
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发表时间：
2011-11-14
期刊：
影响因子：
--
通讯作者：
Gould KL
中科院分区：
文献类型：
--
作者：
Chen JS;Lu LX;Ohi MD;Creamer KM;English C;Partridge JF;Ohi R;Gould KL
在有丝分裂早期，动粒成分Nsk1被CDK1磷酸化，拮抗其在动粒和纺锤体上的定位和功能。CDK1控制着有丝分裂染色体行为和纺锤体微管(MT)动力学的许多方面，以确保准确的染色体分离。在这篇文章中，我们描述了一种新的分裂酵母CDK1的动粒底物Nsk1，它以一种磷酸调节的方式促进了动粒-MT(k-MT)的相互作用和染色体运动。在有丝分裂早期，Nsk1的CDK1磷酸化拮抗Nsk1动粒和纺锤体的定位。一个非磷酸化的Nsk1突变体过早地与动粒和纺锤体结合，粘合了不正确的k-MT连接，并导致高比率的滞后染色体错误分离。因此，缺乏nsk1的细胞会出现合成生长缺陷，突变会扰乱MT动力学和/或动粒结构，而缺乏适当的磷调节会导致更严重的缺陷。有趣的是，Nsk1通过直接与动力蛋白轻链Dlc1结合而稳定下来，而不依赖于动力蛋白马达，并且Nsk1-Dlc1在体外形成链状结构。我们的发现确立了CDK1和Nsk1-Dlc1复合体在调节k-MT界面和染色体分离中的新作用。
Phosphorylation of the kinetochore component Nsk1 by Cdk1 antagonizes its localization to and function at the kinetochore and spindle during early mitosis. Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore–MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis. A nonphosphorylatable Nsk1 mutant binds prematurely to kinetochores and spindle, cementing improper k-MT attachments and leading to high rates of lagging chromosomes that missegregate. Accordingly, cells lacking nsk1 exhibit synthetic growth defects with mutations that disturb MT dynamics and/or kinetochore structure, and lack of proper phosphoregulation leads to even more severe defects. Intriguingly, Nsk1 is stabilized by binding directly to the dynein light chain Dlc1 independently of the dynein motor, and Nsk1–Dlc1 forms chainlike structures in vitro. Our findings establish new roles for Cdk1 and the Nsk1–Dlc1 complex in regulating the k-MT interface and chromosome segregation.
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