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Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex.

BACKGROUND: The actin-related proteins Arp2 and Arp3 are part of a seven-protein complex which is localized in the lamellipodia of a variety of cell types, and in actin-rich spots of unknown function. The Arp2/3 complex enhances actin nucleation and causes branching and crosslinking of actin filaments in vitro; in vivo it is thought to drive the formation of lamellipodia and to be a control center for actin-based motility. The Wiskott-Aldrich syndrome protein, WASP, is an adaptor protein implicated in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Scar1 is a member of a new family of proteins related to WASP, and it may also have a role in regulating the actin cytoskeleton. Scar1 is the human homologue of Dictyostelium Scar1, which is thought to connect G-protein-coupled receptors to the actin cytoskeleton. The mammalian Scar family contains at least four members. We have examined the relationships between WASP, Scar1, and the Arp2/3 complex. RESULTS: We have identified WASP and its relative Scar1 as proteins that interact with the Arp2/3 complex. We have used deletion analysis to show that both WASP and Scar1 interact with the p21 subunit of the Arp2/3 complex through their carboxyl termini. Overexpression of carboxy-terminal fragments of Scar1 or WASP in cells caused a disruption in the localization of the Arp2/3 complex and, concomitantly, induced a complete loss of lamellipodia and actin spots. The induction of lamellipodia by platelet-derived growth factor was also suppressed by overexpression of the fragment of Scar1 that binds to the Arp2/3 complex. CONCLUSIONS: We have identified a conserved sequence domain in proteins of the WASP family that binds to the Arp2/3 complex. Overexpression of this domain in cells disrupts the localization of the Arp2/3 complex and inhibits lamellipodia formation. Our data suggest that WASP-related proteins may regulate the actin cytoskeleton through the Arp2/3 complex.

Pubmed ID: 9889097

Authors

  • Machesky LM
  • Insall RH

Journal

Current biology : CB

Publication Data

March 11, 1999

Associated Grants

None

Mesh Terms

  • 3T3 Cells
  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • Animals
  • Brain Chemistry
  • COS Cells
  • Cytoskeletal Proteins
  • Cytoskeleton
  • Cytosol
  • Gene Expression Regulation
  • Growth Substances
  • Mice
  • Microfilament Proteins
  • Protein Binding
  • Protein Biosynthesis
  • Proteins
  • Rabbits
  • Swine
  • Wiskott-Aldrich Syndrome Protein
  • Wiskott-Aldrich Syndrome Protein Family