The WAVE regulatory complex links diverse receptors to the actin cytoskeleton.

The WAVE regulatory complex links diverse receptors to the actin cytoskeleton.
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DOI:
10.1016/j.cell.2013.11.048
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发表时间:
2014-01-16
期刊:
影响因子:
64.5
通讯作者:
Rosen MK
Rosen MK
中科院分区:
生物学1区
文献类型:
--
作者:
Chen B;Brinkmann K;Chen Z;Pak CW;Liao Y;Shi S;Henry L;Grishin NV;Bogdan S;Rosen MK

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WAVE调节复合物(WRC)通过刺激Arp 2/3复合物在不同膜位点的肌动蛋白成核活性来控制整个细胞的肌动蛋白细胞骨架动力学。然而,招募WRC到特定地点的因素仍然知之甚少。在这里,我们已经确定了一个潜在的WRC配体的大家族,由约120种不同的膜蛋白组成,包括原钙粘蛋白,ROBO,netrin受体,神经连接素,GPCR和通道。结构,生物化学和细胞的研究表明,一种新的序列基序,定义这些配体结合到一个高度保守的相互作用表面的WRC形成的Sra和阿比特龙亚基。在果蝇中,这种结合表面的突变会导致卵子发生过程中肌动蛋白细胞骨架组织和卵子形态的缺陷,从而导致雌性不育。我们的研究结果直接连接不同的膜蛋白的WRC和肌动蛋白细胞骨架,并在后生动物有广泛的生理和病理后果。
The WAVE regulatory complex (WRC) controls actin cytoskeletal dynamics throughout the cell by stimulating the actin nucleating activity of the Arp2/3 complex at distinct membrane sites. However, the factors that recruit the WRC to specific locations remain poorly understood. Here we have identified a large family of potential WRC ligands, consisting of ~120 diverse membrane proteins including protocadherins, ROBOs, netrin receptors, Neuroligins, GPCRs and channels. Structural, biochemical and cellular studies reveal that a novel sequence motif that defines these ligands binds to a highly conserved interaction surface of the WRC formed by the Sra and Abi subunits. Mutating this binding surface in flies resulted in defects in actin cytoskeletal organization and egg morphology during oogenesis, leading to female sterility. Our findings directly link diverse membrane proteins to the WRC and actin cytoskeleton, and have broad physiological and pathological ramifications in metazoans.
DOI: 10.1038/nrm2867
发表时间: 2010-04
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