Nuclear Mitotic Apparatus (NuMA) Interacts with and Regulates Astrin at the Mitotic Spindle
Nuclear Mitotic Apparatus (NuMA) Interacts with and Regulates Astrin at the Mitotic Spindle
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DOI：
10.1074/jbc.m116.724831
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发表时间：
2016-09-16
影响因子：
4.8
通讯作者：
Du, Quansheng
中科院分区：
文献类型：
--
作者：
Chu, Xiaogang;Chen, Xuanyu;Du, Quansheng
大核有丝分裂器（NuMA）蛋白是有丝分裂纺锤体组装和维持的重要参与者。我们在这里报告的鉴定Astrin，纺锤体和kinetochore相关的蛋白质，作为一种新的相互作用的NuMA。我们发现NuMA的C-末端尾部可以直接与Astrin的C末端结合，这种相互作用有助于将Astrin招募到微管中。通过RNA干扰敲低NuMA显著损害了Astrin向有丝分裂纺锤体的募集。过表达哺乳动物同源的果蝇引脚（LGN），它阻断微管结合的NuMA和竞争与Astrin的NuMA结合的N末端，也导致了类似的结果。此外，我们发现细胞质动力蛋白是必需的纺锤极积累的Astrin，和动力蛋白介导的运输是重要的平衡分布的Astrin之间的纺锤极和动粒。另一方面，如果Astrin水平降低，则NuMA不能有效地集中在纺锤体极点。我们的研究结果揭示了有丝分裂进程的两个重要调节因子之间的直接物理联系，并证明了NuMA-Astrin相互作用对准确细胞分裂的关键作用。
The large nuclear mitotic apparatus (NuMA) protein is an essential player in mitotic spindle assembly and maintenance. We report here the identification of Astrin, a spindle- and kinetochore-associated protein, as a novel interactor of NuMA. We show that the C-terminal tail of NuMA can directly bind to the C terminus of Astrin and that this interaction helps to recruit Astrin to microtubules. Knockdown of NuMA by RNA interference dramatically impaired Astrin recruitment to the mitotic spindle. Overexpression of the N terminus of mammalian homologue of Drosophila Pins (LGN), which blocks the microtubule binding of NuMA and competes with Astrin for NuMA binding, also led to similar results. Furthermore, we found that cytoplasmic dynein is required for the spindle pole accumulation of Astrin, and dynein-mediated transport is important for balanced distribution of Astrin between spindle poles and kinetochores. On the other hand, if Astrin levels are reduced, then NuMA could not efficiently concentrate at the spindle poles. Our findings reveal a direct physical link between two important regulators of mitotic progression and demonstrate the critical role of the NuMA-Astrin interaction for accurate cell division.