Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions.

ABSTRACT: 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 mark

SUBMITTER: Wu S 

PROVIDER: S-EPMC3411165 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature