近日，國際學(xué)術(shù)期刊Cell Research在線發(fā)表了中國科學(xué)院生物化學(xué)與細(xì)胞生物學(xué)研究所朱學(xué)良研究組的研究論文 “Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions",。該論文描述Nudel通過結(jié)合Sra1 和HSPC300亞基,，在WAVE復(fù)合物的體內(nèi)組裝過程中發(fā)揮了重要作用。
在真核細(xì)胞中,，微絲這類細(xì)胞骨架對于細(xì)胞遷移,、膜泡運輸、有絲分裂,、細(xì)胞形態(tài)維持和變化等諸多生命活動有著重要的作用,。在細(xì)胞遷移過程中，細(xì)胞的運動前緣有大量的分枝狀微絲在快速地形成和解聚,，形成推動細(xì)胞膜向前移動的動力,。WAVE復(fù)合物是這種分枝狀微絲形成的重要調(diào)控因子。它是由Sra,、Nap,、Abi、WAVE和HSPC300這五個亞基按等比例聚合而成的蛋白質(zhì)異源五聚體,。由于不完整的WAVE復(fù)合物可能會干擾正常的微絲調(diào)控機(jī)制,，因此它的快速組裝很重要，否則容易被降解,。盡管人們已經(jīng)發(fā)現(xiàn)WAVE的亞基會在體外形成一些亞復(fù)合物,，但對其在細(xì)胞內(nèi)組裝的過程和具體機(jī)制卻了解不多。該實驗室的前期研究發(fā)現(xiàn)蛋白質(zhì)Nudel對細(xì)胞遷移是必須的,，并先后揭示了該蛋白質(zhì)通過穩(wěn)定活性形式的Cdc42和新生的粘附結(jié)構(gòu)而促進(jìn)細(xì)胞遷移的機(jī)理,。但是Nudel是否還對微絲系統(tǒng)有作用卻不清楚,。
研究生武爽和同事們發(fā)現(xiàn)，Nudel能夠穩(wěn)定WAVE復(fù)合物中Sra1,、Nap1和Abi1形成的異源三聚體和HSPC300形成的同源三聚體,，并促進(jìn)HSPC300同WAVE2的結(jié)合。利用RNA干擾技術(shù)抑制Nudel的表達(dá)可以引起WAVE復(fù)合物及其亞基的蛋白質(zhì)水平下調(diào),，WAVE復(fù)合物依賴性的微絲聚合也相應(yīng)地受到抑制,，說明Nudel的這些作用有助于WAVE復(fù)合物的體內(nèi)組裝。他們據(jù)此提出了WAVE復(fù)合物在細(xì)胞內(nèi)組裝過程的模型圖,。這些研究結(jié)果為Nudel在細(xì)胞遷移中的功能提供了新的知識,。
該研究項目得到了科技部、國家自然科學(xué)基金委,、上海市科委和中國科學(xué)院的資助,。（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.
