The Wiskott-Aldrich Syndrome Protein Directs Actin-Based Motility by Stimulating Actin Nucleation With the Arp2/3 Complex

Curr Biol. 1999 May 20;9(10):555-8. doi: 10.1016/s0960-9822(99)80243-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin-Related Protein 2
  • Actins / metabolism*
  • Biopolymers
  • Cytoskeletal Proteins*
  • Proteins / metabolism*
  • Wiskott-Aldrich Syndrome / metabolism*
  • Wiskott-Aldrich Syndrome Protein

Substances

  • Actin-Related Protein 2
  • Actins
  • Biopolymers
  • Cytoskeletal Proteins
  • Proteins
  • Wiskott-Aldrich Syndrome Protein