FIGURE 17-16 Regulation of the Arp2/3 complex by WASp and PI(4,5)P₂. The NPF WASp is inactive due to an intramolecular interaction that masks the WCA domain. It is activated by a coincidence detection mechanism: it must bind both the regulatory phospholipid PI(4,5)P₂ though its basic domain (B) and the membrane-bound active small G protein Cdc42-GTP (a member of the Rho family) through its Rho-binding domain (RBD). When activated in this way, the intramolecular interaction in WASp is relieved, allowing the W domain to bind actin and the acidic A domain to activate the Arp2/3 complex. For simplicity, only a single NFP-Arp2/3 interaction is shown. Regulation of the Rho family of small GTPases is detailed in Figures 17-41 and 17-43.