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发动蛋白2在有丝分裂时与微管结合,并调节细胞周期进程。

Dynamin 2 associates with microtubules at mitosis and regulates cell cycle progression.

作者信息

Ishida Nobuhisa, Nakamura Yuichi, Tanabe Kenji, Li Shun-Ai, Takei Kohji

机构信息

Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

出版信息

Cell Struct Funct. 2011;36(2):145-54. doi: 10.1247/csf.10016. Epub 2010 Dec 8.

Abstract

Dynamin, a ~100 kDa large GTPase, is known as a key player for membrane traffic. Recent evidence shows that dynamin also regulates the dynamic instability of microtubules by a mechanism independent of membrane traffic. As microtubules are highly dynamic during mitosis, we investigated whether the regulation of microtubules by dynamin is essential for cell cycle progression. Dynamin 2 intensely localized at the mitotic spindle, and the localization depended on its proline-rich domain (PRD), which is required for microtubule association. The deletion of PRD resulted in the impairment of cytokinesis, whereby the mutant had less effect on endocytosis. Interestingly, dominant-negative dynamin (K44A), which blocks membrane traffic but has no effect on microtubules, also blocked cytokinesis. On the other hand, the deletion of the middle domain, which binds to γ-tubulin, impaired the entry into mitosis. As both deletion mutants had no significant effect on endocytosis, dynamin 2 may participate in cell cycle progression by regulating the microtubules. These data suggest that dynamin may play a key role for cell cycle progression by two distinct pathways, membrane traffic and cytoskeleton.

摘要

发动蛋白是一种分子量约为100 kDa的大型GTP酶,是膜运输的关键因子。最近的证据表明,发动蛋白还通过一种独立于膜运输的机制调节微管的动态不稳定性。由于微管在有丝分裂期间具有高度动态性,我们研究了发动蛋白对微管的调节是否对细胞周期进程至关重要。发动蛋白2强烈定位于有丝分裂纺锤体,其定位依赖于富含脯氨酸的结构域(PRD),这是微管结合所必需的。PRD的缺失导致胞质分裂受损,突变体对胞吞作用的影响较小。有趣的是,显性负性发动蛋白(K44A)虽然阻断膜运输但对微管无影响,也能阻断胞质分裂。另一方面,与γ-微管蛋白结合的中间结构域的缺失会损害细胞进入有丝分裂。由于这两种缺失突变体对胞吞作用均无显著影响,发动蛋白2可能通过调节微管参与细胞周期进程。这些数据表明,发动蛋白可能通过膜运输和细胞骨架这两条不同的途径在细胞周期进程中发挥关键作用。

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