The Wiskott-Aldrich syndrome protein directs actin-based motility by stimulating actin nucleation with the Arp2/3 complex

Actin polymerization at the cell cortex is thought to provide the driving f orce for aspects of cell-shape change and locomotion. To coordinate cellula r movements, the initiation of actin polymerization is tightly regulated, b oth spatially and temporally. The Wiskott-Aldrich syndrome protein (WASP), encoded by the gene that is mutated in the immunodeficiency disorder Wiskot t-Aldrich syndrome [1], has been implicated in the control of actin polymer ization in cells [2-5], The Arp2/3 complex, an actin-nucleating factor that consists of seven polypeptide subunits [6-8], was recently shown to physic ally interact with WASP [9], We sought to determine whether WASP is a cellu lar activator of the Arp2/3 complex and found that WASP stimulates the acti n nucleation activity of the Arp2/3 complex in vitro. Moreover, WASP-coated microspheres polymerized actin, formed actin tails and exhibited actin-bas ed motility in cell extracts, similar to those behaviors displayed by the p athogenic bacterium Listeria monocytogenes, In extracts depleted of the Arp 2/3 complex, WASP-coated microspheres and L. monocytogenes were non-matile and exhibited only residual actin polymerization. These results demonstrate that WASP is sufficient to direct actin-based motility in cell extracts an d that this function is mediated by the Arp2/3 complex. WASP interacts with diverse signaling proteins and may therefore function to couple signal tra nsduction pathways to Arp2/3-complex activation and actin polymerization. ( C) Elsevier Science Ltd ISSN 0960-9822.