EFC/F-BAR proteins and the N-WASP-WIP complex induce membrane curvature-dependent actin polymerization
EFC/F-BAR proteins and the N-WASP-WIP complex induce membrane curvature-dependent actin polymerization
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DOI：
10.1038/emboj.2008.216
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发表时间：
2008-11-05
期刊：
影响因子：
11.4
通讯作者：
Suetsugu, Shiro
中科院分区：
文献类型：
--
作者：
Takano, Kazunari;Toyooka, Kiminori;Suetsugu, Shiro
扩展的Fer-CIP 4同源性（EFC）/FCH-BAR（F-BAR）结构域产生并结合到限定直径的管状膜结构，所述管状膜结构参与内吞囊泡的形成和分裂。Formin结合蛋白17（FBP 17）和Toca-1包含EFC/F-BAR结构域，并与神经Wiskott-奥尔德里奇综合征蛋白（N-WASP）结合，后者将磷脂酰肌醇（4，5）-二磷酸（PIP（2））和Rho家族GTPase Cdc 42连接到Arp 2/3复合物。已知N-WASP-WASP相互作用蛋白（WASP）复合物（细胞中N-WASP的主要形式）可被Toca-1和Cdc 42激活。在这里，我们发现，在存在Toca-1或FBP 17以及不存在Cdc 42和PIP的情况下，N-WASP-β-内酰胺酶复合物介导的肌动蛋白聚合被含磷脂酰丝氨酸的膜激活，这取决于膜曲率（2）。Cdc 42进一步促进了N-WASP-ATP对肌动蛋白聚合的激活作用。Toca-1或FBP 17将N-WASP-β募集到膜上。Toca-1和FBP 17的SH 3结构域附近的保守酸性残基将N-WASP-β定位在空间上靠近膜，以激活肌动蛋白聚合。因此，曲率依赖性肌动蛋白聚合的刺激空间适当的相互作用的EFC/F-BAR蛋白和N-WASP-ESTA复合物与膜。
Extended Fer-CIP4 homology (EFC)/FCH-BAR (F-BAR) domains generate and bind to tubular membrane structures of defined diameters that are involved in the formation and fission of endocytotic vesicles. Formin-binding protein 17 (FBP17) and Toca-1 contain EFC/F-BAR domains and bind to neural Wiskott-Aldrich syndrome protein (N-WASP), which links phosphatidylinositol (4,5)-bisphosphate (PIP(2)) and the Rho family GTPase Cdc42 to the Arp2/3 complex. The N-WASP-WASP-interacting protein (WIP) complex, a predominant form of N-WASP in cells, is known to be activated by Toca-1 and Cdc42. Here, we show that N-WASP-WIP complex-mediated actin polymerization is activated by phosphatidylserine-containing membranes depending on membrane curvature in the presence of Toca-1 or FBP17 and in the absence of Cdc42 and PIP(2). Cdc42 further promoted the activation of actin polymerization by N-WASP-WIP. Toca-1 or FBP17 recruited N-WASP-WIP to the membrane. Conserved acidic residues near the SH3 domain of Toca-1 and FBP17 positioned the N-WASP-WIP to be spatially close to the membrane for activation of actin polymerization. Therefore, curvature-dependent actin polymerization is stimulated by spatially appropriate interactions of EFC/F-BAR proteins and the N-WASP-WIP complex with the membrane.