Regulation of actin assembly by SCAR/WAVE proteins

Regulation of actin assembly by SCAR/WAVE proteins
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DOI:
10.1042/bst0331243
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发表时间:
2005-12-01
影响因子:
3.9
通讯作者:
Insall, RH
Insall, RH
中科院分区:
生物学3区
文献类型:
--
作者:
Ibarra, N;Pollitt, A;Insall, RH

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肌动蛋白重组是一个严格调控的过程,协调复杂的细胞事件,如细胞迁移,趋化性,吞噬作用和粘附,但这些过程的分子机制还没有很好地理解。SCAR(cAMP受体抑制因子)/WAVE [WASP(Wiskott-Aldrich综合征蛋白)-家族verprolin同源蛋白]蛋白是保守的WASP家族细胞骨架调节因子的成员,其通过触发Arp 2/3(肌动蛋白相关蛋白2/3)-依赖性肌动蛋白成核而在肌动蛋白动力学中起关键作用。SCAR/WAVE被认为是由一个五聚体复合物调节的,该复合物还含有Abi(Abi相互作用物)、Nap(Nck相关蛋白)、PIR 121(p53诱导mRNA 121)和HSPC 300(造血干祖细胞300),但该复合物的结构组织及其单个组分对SCAR/WAVE功能调节的贡献仍不清楚。SCAR/WAVE调节的其他特征通过其他相互作用物和不同复合物的发现而突出。很可能SCAR/WAVE复合物的不同组分的组合组装将被证明对于它们在动态肌动蛋白重组中心的作用是至关重要的。
Actin reorganization is a tightly regulated process that co-ordinates complex cellular events, such as cell migration, chemotaxis, phagocytosis and adhesion, but the molecular mechanisms that underlie these processes are not well understood. SCAR (suppressor of cAMP receptor)/WAVE [WASP (Wiskott-Aldrich syndrome protein)-family verprolin homology protein] proteins are members of the conserved WASP family of cytoskeletal regulators, which play a critical role in actin dynamics by triggering Arp2/3 (actin-related protein 2/3)-dependent actin nucleation. SCAR/WAVEs are thought to be regulated by a pentameric complex which also contains Abi (Abi-interactor), Nap (Nck-associated protein), PIR121 (p53-inducible mRNA 121) and HSPC300 (haematopoietic stem progenitor cell 300), but the structural organization of the complex and the contribution of its individual components to the regulation of SCAR/WAVE function remain unclear. Additional features of SCAR/WAVE regulation are highlighted by the discovery of other interactors and distinct complexes. it is likely that the combinatorial assembly of different components of SCAR/WAVE complexes will prove to be vital for their roles at the centre of dynamic actin reorganization.