Fig. 1. Integrin-mediated activation of the Arp2/3 complex. Left, in the absence of integrin engagement or other stimuli, Rac and Cdc42 are held in an inactive GDP-bound state. WAVE-1 exists in an inactive, heterotetrameric complex with HSPC, NAP125 and PIR. Right, integrin ligation triggers the exchange of GDP for GTP. Cdc42 binds and induces a conformational change in WASP that permits it to bind and activate the Arp2/3 complex. Rac and NCK disrupt the WAVE complex, causing it to disassemble and release WAVE in association with HSPC300. WAVE binds and activates the Arp2/3 complex.