Nudel Facilitates WAVE Complex Assembly

Migrating cells form membrane protrusions in the direction of migration called lamellipodia. Such protrusions are propelled by dynamic polymerization and depolymerization of branched filament actin (F-actin). WAVE complex is a key regulator of such F-actin. Dr. ZHU Xueliang’s group at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, showed that Nudel facilitates WAVE complex assembly in vivo through direct interactions with Sra1 and HSPC300, two subunits of the WAVE complex.

 

WAVE complex is a pentameric protein complex consisting of WAVE, Sra, Nap, Abi, and HSPC300. Its activity is under tight regulation in response to extracellular stimuli. To prevent malfunctioning, subunits are quickly degraded unless they form the complex. How the WAVE complex is assembled in vivo, however, is poorly known. The ZHU lab has demonstrated previously that Nudel is essential for cell migration by stabilizing active Cdc42 via an interaction with Cdc42GAP and by strengthening nascent focal adhesions by binding to Paxillin. Here, Dr. WU Shuang and colleagues further showed that Nudel had chaperon-like functions that facilitated the stability of the Sra1-Nap1-Abi1 subcomplex and the HSPC300 oligomer. It also promoted the interaction between HSPC300 and WAVE2. Depletion of Nudel by RNAi reduced the levels of WAVE complex and its subunits, resulting in impaired F-actin formation both in vitro and in vivo. Basing on the results, the researchers also proposed a model to delineate the assembly of WAVE complex in vivo. This work, entitled “Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions”, was published online in Cell research on March 27^th, 2012.

 

This study was supported by grants from the Ministry of Science and Technology, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, and Chinese Academy of Sciences.

 

AUTHOR CONTACT:

ZHU Xueliang

Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

Shanghai, China

Phone: 86-21-54921406; E-mail: xlzhu@sibs.ac.cn

 

A model for roles of Nudel in the Wave complex assembly in vivo.

(A) Nudel binds to the Sra1-Nap1-Abi1 subcomplex and prevents its degradation.

(B) Nudel interacts with and stabilizes HSPC300 by preventing the dissociation of the monomer from the trimer.

(C) Possible assembly paths of the WAVE complex.