Millard Thomas H, Sharp Stewart J, Machesky Laura M
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Biochem J. 2004 May 15;380(Pt 1):1-17. doi: 10.1042/BJ20040176.
The assembly of a branched network of actin filaments provides the mechanical propulsion that drives a range of dynamic cellular processes, including cell motility. The Arp2/3 complex is a crucial component of such filament networks. Arp2/3 nucleates new actin filaments while bound to existing filaments, thus creating a branched network. In recent years, a number of proteins that activate the filament nucleation activity of Arp2/3 have been identified, most notably the WASP (Wiskott-Aldrich syndrome protein) family. WASP-family proteins activate the Arp2/3 complex, and consequently stimulate actin assembly, in response to extracellular signals. Structural studies have provided a significant refinement in our understanding of the molecular detail of how the Arp2/3 complex nucleates actin filaments. There has also been much progress towards an understanding of the complicated signalling processes that regulate WASP-family proteins. In addition, the use of gene disruption in a number of organisms has led to new insights into the specific functions of individual WASP-family members. The present review will discuss the Arp2/3 complex and its regulators, in particular the WASP-family proteins. Emphasis will be placed on recent developments in the field that have furthered our understanding of actin dynamics and cell motility.
肌动蛋白丝分支网络的组装提供了驱动一系列动态细胞过程（包括细胞运动）的机械推进力。Arp2/3复合物是此类丝网络的关键组成部分。Arp2/3在与现有丝结合时会成核新的肌动蛋白丝，从而形成分支网络。近年来，已鉴定出许多激活Arp2/3丝成核活性的蛋白质，最著名的是WASP（威斯科特-奥尔德里奇综合征蛋白）家族。WASP家族蛋白响应细胞外信号激活Arp2/3复合物，从而刺激肌动蛋白组装。结构研究极大地完善了我们对Arp2/3复合物如何使肌动蛋白丝成核的分子细节的理解。在理解调节WASP家族蛋白的复杂信号传导过程方面也取得了很大进展。此外，在许多生物体中使用基因敲除已使人们对各个WASP家族成员的特定功能有了新的认识。本综述将讨论Arp2/3复合物及其调节剂，特别是WASP家族蛋白。重点将放在该领域的最新进展上，这些进展加深了我们对肌动蛋白动力学和细胞运动的理解。
