WASPfamily

WASP family, or the WASP family of proteins, is a conserved group of actin-nucleation promoting factors that stimulate the Arp2/3 complex to nucleate branched actin filaments. Members include WASP, N-WASP, the WAVE/SCAR proteins, WASH, WHAMM, and JMY. These proteins share a C-terminal verprolin-homology, central, acidic (VCA) region that activates Arp2/3, and N-terminal regulatory regions that control autoinhibition and localization through interactions with small GTPases and adaptor proteins. Many members contain WH1/EVH1 domains and proline-rich regions that mediate protein interactions.

Activation and regulation: In WASP and N-WASP, autoinhibition is relieved by binding of Cdc42-GTP and SH3-domain-containing partners, exposing the VCA region to activate Arp2/3. In WAVE proteins, activity is controlled by the WAVE regulatory complex, integrating signals from Rac, adhesion, and phosphoinositides. Other family members have distinct regulatory inputs but generally promote actin assembly at membranes or endosomes.

Biological roles: WASP family proteins coordinate cytoskeletal remodeling during endocytosis, vesicular trafficking, cell migration, cytokinesis, and immune cell function. They localize to plasma membranes, endosomes, the Golgi network, and the nucleus in some contexts.

Clinical and evolutionary notes: Mutations in WAS cause Wiskott-Aldrich syndrome, a combined immunodeficiency with eczema and thrombocytopenia. Other family members have been linked to neurological and developmental phenotypes in model organisms. The family is widely conserved across eukaryotes, reflecting a central role in actin dynamics.