Cofilin promotes rapid actin filament turnover in vivo
Cofilin promotes rapid actin filament turnover in vivo
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DOI：
10.1038/40418
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发表时间：
1997-07-03
期刊：
影响因子：
64.8
通讯作者：
Drubin, DG
中科院分区：
文献类型：
--
作者：
Lappalainen, P;Drubin, DG
肌动蛋白丝在细胞形态发生和运动中起作用的能力与它们快速组装和拆卸的能力相关联。由于体外分解比体内分解慢得多，因此长期以来一直认为存在刺激分解的细胞因子。虽然许多蛋白质可以影响肌动蛋白的动力学在体外，在体内的相关性，这些影响的演示尚未实现。我们使用遗传学和酵母中的肌动蛋白抑制剂来证明肌动蛋白组装和拆卸的快速循环依赖于小肌动蛋白结合蛋白cofilin，并且cofilin刺激细丝拆卸。这些结果可以解释为什么cofilin在真核生物中普遍存在，并且对于其功能已被遗传测试的每种生物的生存能力至关重要。在体内的cofilin突变体的拆卸缺陷的幅度被发现与在体外观察到的拆卸缺陷的幅度密切相关，支持我们的结论。此外，这些cofilin突变体提供了一个机会，区分在活细胞中的肌动蛋白功能，特别是依赖于丝周转（内吞作用），从那些不（皮层肌动蛋白补丁运动）。
The ability of actin filaments to function in cell morphogenesis and motility is coupled to their capacity for rapid assembly and disassembly. Because disassembly in vitro is much slower than in vivo, cellular factors that stimulate disassembly have long been assumed to exist. Although numerous proteins can affect actin dynamics in vitro, demonstration of in vivo relevance of these effects has not been achieved. We have used genetics and an actin-inhibitor in yeast to demonstrate that rapid cycles of actin assembly and disassembly depend on the small actin-binding protein cofilin, and that cofilin stimulates filament disassembly. These results may explain why cofilin is ubiquitous in eukaryotes and is essential for viability in every organism in which its function has been tested genetically. Magnitudes of disassembly defects in cofilin mutants in vivo were found to be correlated closely with the magnitudes of disassembly defects observed in vitro, supporting our conclusions. Furthermore, these cofilin mutants provided an opportunity to distinguish in living cells those actin functions that depend specifically on filament turnover (endocytosis) from those that do not (cortical actin patch motility).