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 force for aspects of cell-shape change and locomotion. To coordinate cellular movements, the initiation of actin polymerization is tightly regulated, both spatially and temporally. The Wiskott-Aldrich syndrome protein (WASP), encoded by the gene that is mutated in the immunodeficiency disorder Wiskott-Aldrich syndrome [1], has been implicated in the control of actin polymerization in cells [2] [3] [4] [5]. The Arp2/3 complex, an actin-nucleating factor that consists of seven polypeptide subunits [6] [7] [8], was recently shown to physically interact with WASP [9]. We sought to determine whether WASP is a cellular activator of the Arp2/3 complex and found that WASP stimulates the actin nucleation activity of the Arp2/3 complex in vitro. Moreover, WASP-coated microspheres polymerized actin, formed actin tails and exhibited actin-based motility in cell extracts, similar to those behaviors displayed by the pathogenic bacterium Listeria monocytogenes. In extracts depleted of the Arp2/3 complex, WASP-coated microspheres and L. monocytogenes were non-motile and exhibited only residual actin polymerization. These results demonstrate that WASP is sufficient to direct actin-based motility in cell extracts and that this function is mediated by the Arp2/3 complex. WASP interacts with diverse signaling proteins and may therefore function to couple signal transduction pathways to Arp2/3-complex activation and actin polymerization.
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Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
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D051377:Actin-Related Protein 2; D000199:Actins / Q000378:metabolism*; D001704:Biopolymers; D003598:Cytoskeletal Proteins; D011506:Proteins / Q000378:metabolism*; D014923:Wiskott-Aldrich Syndrome / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein
D051377:Actin-Related Protein 2; D000199:Actins; D001704:Biopolymers; D003598:Cytoskeletal Proteins; D011506:Proteins; D051316:Wiskott-Aldrich Syndrome Protein