WAVE regulatory complex

The proteins within the WRC form a CYFIP1-Nap1 heterodimer and a WAVE1-Abi2-HSPC300 heterotrimer,^[1][2] and following interaction with Rac1, the holocomplex has been observed in a CYFIP1-Nap1-Abi2 heterotrimer subcomplex and an active WAVE1-HSPC300 heterodimer subcomplex.^[3]

WRC recruitment to the sites of actin nucleation events at the cell periphery is mediated by the binding of a number of ligands containing a conserved WRC interacting receptor sequence (WIRS) which binds to a conserved location shared across the surfaces of Abi2 and CYFIP1.^[4][5][6] The WRC is activated by interaction with the Rac1 (via the CYFIP1 component of the complex) and Arf small GTPases^[1] (such as ARF1, ARF5, and ARF6^[7] ) or the similar protein ARL1,^[2] which causes dissociation of the CYFIP1-Nap1-Abi2 heterotrimer at the membrane periphery.^[3] This allows the V domain of the WAVE1 component to interact with the actin monomers while its CA domain interacts with the Arp2/3 complex, allowing the Arp2/3 complex to act as a nucleation core for the branching and extension of actin filaments.