F-actin dismantling through a redox-driven synergy between Mical and cofilin.
F-actin dismantling through a redox-driven synergy between Mical and cofilin.
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DOI：
10.1038/ncb3390
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发表时间：
2016-08
影响因子：
21.3
通讯作者：
Reisler E
中科院分区：
文献类型：
--
作者：
Grintsevich EE;Yesilyurt HG;Rich SK;Hung RJ;Terman JR;Reisler E
许多细胞功能依赖于肌动蛋白丝（F-actin）的分解。最具特征的拆卸蛋白，ADF/cofilins/twinstar，切断细丝和回收单体，以促进肌动蛋白组装。Cofilin也是一种相对较弱的肌动蛋白解聚剂，对细胞F-肌动蛋白不稳定的机制提出了疑问。在这里，我们发现了一个关键环节，有针对性的F-肌动蛋白拆卸发现，F-肌动蛋白是有效地拆除通过翻译后介导的协同作用之间的cofilin和肌动蛋白氧化酶Mical。我们发现，Mical介导的肌动蛋白氧化提高了cofilin与细丝的结合，与单独的效应物相比，它们的联合作用大大加速了F-肌动蛋白的分解。这种协同作用对于体内F-肌动蛋白分解也是必要和充分的，放大了Mical和cofilin对细胞重塑、轴突引导和脑信号蛋白/丛状蛋白排斥的作用。因此，Mical和cofilin形成氧化还原依赖性协同对，其通过快速分解F-肌动蛋白并产生具有改变的组装性质的后修饰的肌动蛋白来促进F-肌动蛋白不稳定性。
Numerous cellular functions depend on actin filament (F-actin) disassembly. The best-characterized disassembly proteins, the ADF/cofilins/twinstar, sever filaments and recycle monomers to promote actin assembly. Cofilin is also a relatively weak actin disassembler, posing questions about mechanisms of cellular F-actin destabilization. Here we uncover a key link to targeted F-actin disassembly by finding that F-actin is efficiently dismantled through a post-translational-mediated synergism between cofilin and the actin-oxidizing enzyme Mical. We find that Mical-mediated oxidation of actin improves cofilin binding to filaments, where their combined effect dramatically accelerates F-actin disassembly compared to either effector alone. This synergism is also necessary and sufficient for F-actin disassembly in vivo, magnifying the effects of both Mical and cofilin on cellular remodeling, axon guidance, and Semaphorin/Plexin repulsion. Mical and cofilin, therefore, form a Redox-dependent synergistic pair that promotes F-actin instability by rapidly dismantling F-actin and generating post-translationally modified actin that has altered assembly properties.