WASP and WAVE Family Protein Complexes
Arp2/3 is inactive and is unable to trigger de novo actin polymerization. It must be activated by binding to members of the WASP/WAVE family of scaffold proteins to effectively stimulate actin polymerization. The WASP/WAVE family members (WASP, N-WASP, WAVE-1, WAVE-2, and WAVE-3) are activated by Cdc42 and Rac. Thus, a linear pathway (Cdc42/Rac→WASP/WAVE→Arp2/3) translates cellular cues into the assembly of actin filaments. Protein complexes organized by the WASP/WAVE proteins, however, modulate this basic pathway. This chapter summarizes how the WASP and WAVE family protein complexes are organized and are thought to function. WASP/N-WASP and WAVE proteins function as scaffolds to organize protein complexes that modulate dynamic actin turnover through Arp2/3. These protein complexes serve to optimize subcellular targeting of WASP/WAVE, and to act as positive and negative feedback information loops to regulate actin dynamics. Thus, these complexes are likely to serve as sophisticated non-linear signaling pathways that function between Rho-GTPases and Arp2/3. Components of the WASP and WAVE complexes may also function to tie actin regulation to other pathways by interacting with separate protein complexes. Finally, it is likely that new regulatory complexes await discovery. In this regard, WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) has recently been identified as a potential new member of the WASP/WAVE family of Arp2/3 activators.
