Regulation of actin dynamics by WASP and WAVE family proteins

Signal-dependent regulation of actin dynamics is essential for a variety of cellular processes, including formation of the membrane protrusions required for cell locomotion. Wiskott-Aldrich syndrome protein (WASP), neural (N)-WASP and WASP family verprolin-homologous (WAVE, also named Scar) proteins are thought to play a role in these processes by relaying activation signals from small GTPases, such as Cdc42 and Rac, to the actin-nucleating complex Arp2/3. Although much biochemical and structural biological work has defined the paradigms through which WASP and N-WASP regulation is achieved, only recently have the mechanisms that control WAVE proteins begun to be clarified. WAVE proteins assemble into macromolecular complexes, which are essential for the regulation of WAVE nucleation-promoting activity, dynamic localization and stability. In this article, we discuss recent studies that highlight novel modalities through which WAVE proteins are regulated and, in turn, mediate the site-directed actin polymerization required for membrane protrusion, thus enabling cell motility.