Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation
Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation
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DOI：
10.1016/s0960-9822(01)00098-7
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发表时间：
2001-03-06
期刊：
影响因子：
9.2
通讯作者：
Cooper, JA
中科院分区：
文献类型：
--
作者：
Weaver, AM;Karginov, AV;Cooper, JA
corneum是一种c-src底物，与迁移细胞前沿的动态肌动蛋白组装位点相关。我们以前表明，corneum结合Arp 2/3复合物，成核肌动蛋白丝组装的基本分子机器。在这项研究中，我们证明，corneum激活Arp 2/3复合物的基础上直接可视化的细丝网络和芘肌动蛋白测定。引人注目的是，coronin有效地抑制了纤维网络的去支化。当corneum与N-WASp的活性VCA片段组合加入时，它们协同增强Arp 2/3诱导的肌动蛋白丝分支。Corprin的N端酸性结构域和F端肌动蛋白结合结构域是激活Arp 2/3复合物所必需的。这些结果支持了一个模型，其中corneum调节肌动蛋白丝树突成核的两种机制，（1）直接激活Arp 2/3复合物和（2）稳定新产生的丝分支点。通过这些机制，coronin可以促进肌动蛋白网络的形成和稳定，从而驱动迁移细胞前缘的突起。(C)2001爱思唯尔科技有限公司版权所有。
Cortactin is a c-src substrate associated with sites of dynamic actin assembly at the leading edge of migrating cells. We previously showed that cortactin binds to Arp2/3 complex, the essential molecular machine for nucleating actin filament assembly. In this study, we demonstrate that cortactin activates Arp2/3 complex based on direct visualization of filament networks and pyrene actin assays. Strikingly, cortactin potently inhibited the debranching of filament networks. When cortactin was added in combination with the active VCA fragment of N-WASp, they synergistically enhanced Arp2/3-induced actin filament branching. The N-terminal acidic and F-actin binding domains of cortactin were both necessary to activate Arp2/3 complex. These results support a model in which cortactin modulates actin filament dendritic nucleation by two mechanisms, (1) direct activation of Arp2/3 complex and (2) stabilization of newly generated filament branch points. By these mechanisms, cortactin may promote the formation and stabilization of the actin network that drives protrusion at the leading edge of migrating cells. (C) 2001 Elsevier Science Ltd. All rights reserved.