近日，国际学术期刊Cell Research在线发表了中国科学院生物化学与细胞生物学研究所朱学良研究组的研究论文 “Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions"。该论文描述Nudel通过结合Sra1 和HSPC300亚基，在WAVE复合物的体内组装过程中发挥了重要作用。
在真核细胞中，微丝这类细胞骨架对于细胞迁移、膜泡运输、有丝分裂、细胞形态维持和变化等诸多生命活动有着重要的作用。在细胞迁移过程中，细胞的运动前缘有大量的分枝状微丝在快速地形成和解聚，形成推动细胞膜向前移动的动力。WAVE复合物是这种分枝状微丝形成的重要调控因子。它是由Sra、Nap、Abi、WAVE和HSPC300这五个亚基按等比例聚合而成的蛋白质异源五聚体。由于不完整的WAVE复合物可能会干扰正常的微丝调控机制，因此它的快速组装很重要，否则容易被降解。尽管人们已经发现WAVE的亚基会在体外形成一些亚复合物，但对其在细胞内组装的过程和具体机制却了解不多。该实验室的前期研究发现蛋白质Nudel对细胞迁移是必须的，并先后揭示了该蛋白质通过稳定活性形式的Cdc42和新生的粘附结构而促进细胞迁移的机理。但是Nudel是否还对微丝系统有作用却不清楚。
研究生武爽和同事们发现，Nudel能够稳定WAVE复合物中Sra1、Nap1和Abi1形成的异源三聚体和HSPC300形成的同源三聚体，并促进HSPC300同WAVE2的结合。利用RNA干扰技术抑制Nudel的表达可以引起WAVE复合物及其亚基的蛋白质水平下调，WAVE复合物依赖性的微丝聚合也相应地受到抑制，说明Nudel的这些作用有助于WAVE复合物的体内组装。他们据此提出了WAVE复合物在细胞内组装过程的模型图。这些研究结果为Nudel在细胞迁移中的功能提供了新的知识。
该研究项目得到了科技部、国家自然科学基金委、上海市科委和中国科学院的资助。（生物谷Bioon.com）
doi:10.1038/cr.2012.47
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Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions
Shuang Wu, Li Ma, Yibo Wu, Rong Zeng and Xueliang Zhu
The WAVE regulatory complex (WRC), consisting of WAVE, Sra, Nap, Abi, and HSPC300, activates the Arp2/3 complex to control branched actin polymerization in response to Rac activation. How the WRC is assembled in vivo is not clear. Here we show that Nudel, a protein critical for lamellipodia formation, dramatically stabilized the Sra1-Nap1-Abi1 complex against degradation in cells through a dynamic binding to Sra1, whereas its physical interaction with HSPC300 protected free HSPC300 from the proteasome-mediated degradation and stimulated the HSPC300-WAVE2 complex formation. By contrast, Nudel showed little or no interactions with the Sra1-Nap1-Abi1-WAVE2 and the Sra1-Nap1-Abi1-HSPC300 complexes as well as the mature WRC. Depletion of Nudel by RNAi led to general subunit degradation and markedly attenuated the levels of mature WRC. It also abolished the WRC-dependent actin polymerization in vitro and the Rac1-induced lamellipodial actin network formation during cell spreading. Therefore, Nudel is important for the early steps of the WRC assembly in vivo by antagonizing the instability of certain WRC subunits and subcomplexes.
