Figure 1.

Factors known to regulate NWASP and WRC (A) N-WASP exists in an auto-inhibited state, with its Arp2/3-activating VCA domain bound to the GTPase binding domain (GBD). Binding of PtdIns(4,5)P2 to the polybasic (B) region, and active Cdc42 (GTP bound) to the GBD releases the VCA domain, allowing it to bind the Arp2/3 complex and initiate actin polymerization. (B) Similarly, the VCA domain of WAVE is also concealed, as it is bound to Sra1 within the WRC, rendering the complex inactive. Numerous factors such as binding of GTP-loaded Rac1 to Sra1, binding of PtdIns(3,4,5)P3 to the polybasic (B) domain, and the binding of IRSp53 (and other SH3 containing proteins) to the poly-proline region of WAVE, have been implicated in WRC activation, potentiating actin polymerization.