Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska) complex to kinetochores.
Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska) complex to kinetochores.
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DOI：
10.1242/bio.026930
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发表时间：
2017-11-15
期刊：
影响因子：
2.4
通讯作者：
Gorbsky GJ
中科院分区：
文献类型：
--
作者：
Sivakumar S;Gorbsky GJ
动粒在动态纺锤体微管上移动染色体并调节纺锤体检查点的信号传导。纺锤体和运动编排相关（Ska）复合物，由Ska1，Ska2和Ska3的两个拷贝组成的六聚体，与这两种作用有关。被充分研究的有丝分裂激酶Cdk 1、Aurora B、Plk 1、Mps 1和Bub 1磷酸化的动粒组分调节染色体运动和检查点信号。相反的磷酸酶的作用更不明确。最近，我们发现Ska1的C末端募集蛋白磷酸酶1（PP1）到着丝粒。在这里，我们表明，PP1和蛋白磷酸酶2A（PP2A）都促进积累的Ska在着丝粒。通过siRNA消耗PP1或PP2A减少了着丝粒处的Ska结合，损害了染色体与纺锤体中平面的对齐，并导致中期延迟或停滞，这些表型也在Ska消耗后观察到。PP1与外部动粒蛋白Nuf2的人工拴系促进了Ska向动粒的募集，并且它减少了但不能完全挽救在Ska耗尽后看到的染色体排列和中期停滞缺陷。我们建议，斯卡有多种功能，促进有丝分裂的进展和着丝粒相关磷酸酶的功能，在一个正反馈循环，以加强斯卡复杂的积累在着丝粒。总结：蛋白磷酸酶与纺锤体和着丝粒相关（Ska）复合体之间的反馈调节染色体运动和细胞周期中期到后期的转换。这篇文章有一个相关的第一人称采访的第一作者的文件作为补充信息的一部分。
Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The spindle- and kinetochore-associated (Ska) complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1) to kinetochores. Here we show that PP1 and protein phosphatase 2A (PP2A) both promote accumulation of Ska at kinetochores. Depletion of PP1 or PP2A by siRNA reduces Ska binding at kinetochores, impairs alignment of chromosomes to the spindle midplane, and causes metaphase delay or arrest, phenotypes that are also seen after depletion of Ska. Artificial tethering of PP1 to the outer kinetochore protein Nuf2 promotes Ska recruitment to kinetochores, and it reduces but does not fully rescue chromosome alignment and metaphase arrest defects seen after Ska depletion. We propose that Ska has multiple functions in promoting mitotic progression and that kinetochore-associated phosphatases function in a positive feedback cycle to reinforce Ska complex accumulation at kinetochores. Summary: Feedback between protein phosphatases and the spindle- and kinetochore-associated (Ska) complex regulates chromosome movement and the metaphase-to-anaphase cell cycle transition. This article has an associated First Person interview with the first author of the paper as part of the supplementary information.
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影响因子：
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