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微管控制应激颗粒的移动性和动态变化。

Microtubules govern stress granule mobility and dynamics.

作者信息

Nadezhdina Elena S, Lomakin Alexis J, Shpilman Alexey A, Chudinova Elena M, Ivanov Pavel A

机构信息

Institute of Protein Research of the Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia.

出版信息

Biochim Biophys Acta. 2010 Mar;1803(3):361-71. doi: 10.1016/j.bbamcr.2009.12.004. Epub 2009 Dec 28.

DOI:10.1016/j.bbamcr.2009.12.004
PMID:20036288
Abstract

Stress granules (SGs) are ribonucleoprotein (RNP)-containing assemblies that are formed in the cytoplasm in response to stress. Previously, we demonstrated that microtubule depolymerization inhibited SG formation. Here, we show that arsenate-induced SGs move throughout the cytoplasm in a microtubule-dependent manner, and microtubules are required for SG disassembly, but not for SG persistence. Analysis of SG movement revealed that SGs exhibited obstructed diffusion on an average, though sometimes SGs demonstrated rapid displacements. Microtubule depolymerization did not influence preformed SG number and size, but significantly reduced the average velocity of SG movement, the frequency of quick movement events, and the apparent diffusion coefficient of SGs. Actin filament disruption had no effect on the SG motility. In cycloheximide-treated cells SGs dissociated into constituent parts that then dissolved within the cytoplasm. Microtubule depolymerization inhibited cycloheximide-induced SG disassembly. However, microtubule depolymerization did not influence the dynamics of poly(A)-binding protein (PABP) in SGs, according to FRAP results. We suggest that the increase of SG size is facilitated by the transport of smaller SGs along microtubules with subsequent fusion of them. At least some protein components of SGs can exchange with the cytoplasmic pool independently of microtubules.

摘要

应激颗粒(SGs)是一种含核糖核蛋白(RNP)的聚集体,在应激反应时于细胞质中形成。此前,我们证明微管解聚可抑制SG形成。在此,我们表明砷酸盐诱导的SGs以微管依赖的方式在整个细胞质中移动,微管是SGs解体所必需的,但不是SGs持续存在所必需的。对SG移动的分析表明,SGs平均表现出受阻扩散,不过有时SGs会有快速位移。微管解聚不影响预先形成的SG的数量和大小,但显著降低了SG移动的平均速度、快速移动事件的频率以及SGs的表观扩散系数。肌动蛋白丝破坏对SG的运动性没有影响。在环己酰亚胺处理的细胞中,SGs解离成组成部分然后在细胞质中溶解。微管解聚抑制了环己酰亚胺诱导的SG解体。然而,根据荧光恢复后光漂白(FRAP)结果显示,微管解聚不影响SGs中多聚腺苷酸结合蛋白(PABP)的动态变化。我们认为较小的SGs沿微管运输并随后融合促进了SG大小的增加。SGs的至少一些蛋白质成分可独立于微管与细胞质池进行交换。

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