WAVE regulatory complex.
WAVE regulatory complex.
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DOI：
10.1016/j.cub.2021.01.086
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发表时间：
2021-05-24
期刊：
影响因子：
--
通讯作者：
Chen B
中科院分区：
文献类型：
--
作者：
Rottner K;Stradal TEB;Chen B
肌动蛋白细胞骨架的动态重排驱动真核细胞中的无数过程，例如细胞迁移和囊泡运输，其失调与多种疾病密切相关，包括癌症、免疫缺陷和神经系统疾病。 Wiskott-Aldrich 综合征蛋白 (WASP) 家族的成员，包括 WASP、N-WASP、WAVE、WASH、WHAMM、JMY 和最近发现的 WHIMP，是普遍存在的肌动蛋白动力学调节因子。尽管每个 WASP 家族蛋白使用不同的调节机制并参与不同的细胞过程，但它们都通过整合各种上游信号并将其传输到其羧基末端 WCA（WH2-central-acidic，其中 WH2 代表 WASP 同源 2）结构域来发挥作用。该结构域刺激 Arp2/3 复合物的肌动蛋白成核活性，促进现有丝形成新丝，从而形成对膜动态变形至关重要的分支肌动蛋白网络。
Dynamic rearrangement of the actin cytoskeleton drives a myriad of processes in eukaryotic cells, such as cell migration and vesicle trafficking, and its dysregulation is deeply associated with various diseases, including cancer, immune deficiency, and neurological disorders. Members of the Wiskott-Aldrich syndrome protein (WASP) family, including WASP, N-WASP, WAVE, WASH, WHAMM, JMY, and the recently identified WHIMP, are ubiquitous regulators of actin dynamics. Although each WASP-family protein uses a different regulatory mechanism and participates in distinct cellular processes, they all act by integrating various upstream signals and transmitting them to their carboxy-terminal WCA (WH2-central-acidic, where WH2 stands for WASP homology 2) domain. This domain stimulates the actin nucleation activity of the Arp2/3 complex to promote the formation of new filaments from existing ones, creating branched actin networks that are crucial for dynamic deformations of membranes.