WAVE regulatory complex

Abstract

Dynamic rearrangement of the actin cytoskeleton drives a myriad of processes in eukaryotic cells, such as cell migration and vesicle trafficking, and its dysregulation is deeply associated with various diseases, including cancer, immune deficiency, and neurological disorders. Members of the Wiskott-Aldrich syndrome protein (WASP) family, including WASP, N-WASP, WAVE, WASH, WHAMM, JMY, and the recently identified WHIMP, are ubiquitous regulators of actin dynamics. Although each WASP-family protein uses a different regulatory mechanism and participates in distinct cellular processes, they all act by integrating various upstream signals and transmitting them to their carboxy-terminal WCA (WH2-central-acidic, where WH2 stands for WASP homology 2) domain. This domain stimulates the actin nucleation activity of the Arp2/3 complex to promote the formation of new filaments from existing ones, creating branched actin networks that are crucial for dynamic deformations of membranes.