Enhancement of branching efficiency by the actin filament-binding activity of N-WASP/WAVE2.

Abstract

The actin-related protein (Arp) 2/3 complex is an essential regulator of de novo actin filament formation. Arp2/3 nucleates the polymerization of actin and creates branched actin filaments when activated by Arp2/3-complex activating domain (VCA) of Wiskott-Aldrich syndrome proteins (WASP family proteins). We found that the branching of actin filaments on pre-existing ADP filaments mediated by the Arp2/3 complex is twice as efficient when Arp2/3 was activated by wild-type neural WASP (N-WASP) or WASP-family verprolin-homologous protein (WAVE) 2 than when activated by the VCA domain alone. By contrast, there was no difference between wild-type N-WASP or WAVE2 and VCA in the branching efficiency on de novo filaments, which are thought to consist mainly of ADP-phosphate filaments. This increased branching efficiency on ADP filaments is due to the basic region located in the center of N-WASP and WAVE2, which was found to associate with ADP actin filaments. Actin filaments and phosphatidylinositol bisphosphate (PIP2) associate with N-WASP at different sites. This association of N-WASP and WAVE2 with actin filaments enhanced recruitment of Arp2/3 to the pre-existing filaments, presumably leading to efficient nucleation and branch formation on pre-existing filaments. These data together suggest that the actin filament binding activity of N-WASP and WAVE2 in the basic region increases the number of barbed ends created on pre-existing filaments. Efficient branching on ADP filaments may be important for initiation of actin-based motility.

• Authors: S Suetsugu, H Miki, H Yamaguchi, T Obinata, T Takenawa
• Journal: Journal of cell science (J Cell Sci) Vol. 114 Issue Pt 24 Pg. 4533-42 (Dec 2001) ISSN: 0021-9533 [Print] England
• PMID: 11792818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actin-Related Protein 2
• Actin-Related Protein 3
• Actins
• Cytoskeletal Proteins
• Microfilament Proteins
• Nerve Tissue Proteins
• Phosphatidylinositol 4,5-Diphosphate
• Wiskott-Aldrich Syndrome Protein, Neuronal

Topics

• Actin Cytoskeleton (metabolism)
• Actin-Related Protein 2
• Actin-Related Protein 3
• Actins (metabolism, physiology)
• Animals
• Cytoskeletal Proteins
• Microfilament Proteins (genetics, metabolism, physiology)
• Nerve Tissue Proteins (genetics, metabolism, physiology)
• Phosphatidylinositol 4,5-Diphosphate (physiology)
• Protein Binding (genetics)
• Protein Structure, Tertiary (genetics)
• Rabbits
• Wiskott-Aldrich Syndrome (metabolism)
• Wiskott-Aldrich Syndrome Protein, Neuronal