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PCM1 将 Plk1 招募到中心体周围基质中,以促进有丝分裂进入前初级纤毛的解体。

PCM1 recruits Plk1 to the pericentriolar matrix to promote primary cilia disassembly before mitotic entry.

机构信息

MOE Key Laboratory of Cell Proliferation and Differentiation and State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.

出版信息

J Cell Sci. 2013 Mar 15;126(Pt 6):1355-65. doi: 10.1242/jcs.114918. Epub 2013 Jan 23.

Abstract

Primary cilia, which emanate from the cell surface, exhibit assembly and disassembly dynamics along the progression of the cell cycle. However, the mechanism that links ciliary dynamics and cell cycle regulation remains elusive. In the present study, we report that Polo-like kinase 1 (Plk1), one of the key cell cycle regulators, which regulate centrosome maturation, bipolar spindle assembly and cytokinesis, acts as a pivotal player that connects ciliary dynamics and cell cycle regulation. We found that the kinase activity of centrosome enriched Plk1 is required for primary cilia disassembly before mitotic entry, wherein Plk1 interacts with and activates histone deacetylase 6 (HDAC6) to promote ciliary deacetylation and resorption. Furthermore, we showed that pericentriolar material 1 (PCM1) acts upstream of Plk1 and recruits the kinase to pericentriolar matrix (PCM) in a dynein-dynactin complex-dependent manner. This process coincides with the primary cilia disassembly dynamics at the onset of mitosis, as depletion of PCM1 by shRNA dramatically disrupted the pericentriolar accumulation of Plk1. Notably, the interaction between PCM1 and Plk1 is phosphorylation dependent, and CDK1 functions as the priming kinase to facilitate the interaction. Our data suggest a mechanism whereby the recruitment of Plk1 to pericentriolar matrix by PCM1 plays a pivotal role in the regulation of primary cilia disassembly before mitotic entry. Thus, the regulation of ciliary dynamics and cell proliferation share some common regulators.

摘要

纤毛从细胞表面伸出,沿着细胞周期的进程表现出组装和拆卸的动态变化。然而,将纤毛动力学与细胞周期调控联系起来的机制仍不清楚。在本研究中,我们报告称,Polo 样激酶 1(Plk1)是细胞周期调控的关键因子之一,它调节中心体成熟、双极纺锤体组装和胞质分裂,是连接纤毛动力学和细胞周期调控的关键因子。我们发现,进入有丝分裂前,富含中心体的 Plk1 的激酶活性对于初级纤毛的解体是必需的,其中 Plk1 与组蛋白去乙酰化酶 6(HDAC6)相互作用并激活后者,以促进纤毛去乙酰化和吸收。此外,我们表明,中心体周围物质 1(PCM1)作为 Plk1 的上游因子,以依赖于动力蛋白-动力蛋白激活复合物的方式将激酶募集到中心体周围基质(PCM)。这个过程与有丝分裂起始时初级纤毛的解体动力学相吻合,因为 shRNA 敲低 PCM1 会严重破坏 Plk1 在中心体周围的积累。值得注意的是,PCM1 和 Plk1 之间的相互作用依赖于磷酸化,CDK1 作为启动激酶促进了相互作用。我们的数据表明,PCM1 将 Plk1 募集到中心体周围基质的机制在有丝分裂前初级纤毛解体的调控中起着关键作用。因此,纤毛动力学和细胞增殖的调控共享一些共同的调节因子。

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