Direct binding of the verprolin-homology domain in N-WASP to actin is essential for cytoskeletal reorganization

Biochem Biophys Res Commun. 1998 Feb 4;243(1):73-8. doi: 10.1006/bbrc.1997.8064.


Verprolin is a yeast protein whose inactivation leads to a cytoskeletal defect characterized by the abnormal organization of actin filaments. Recently, two mammalian proteins previously shown to regulate the actin cytoskeleton, Wiskott-Aldrich Syndrome Protein (WASP) and its homolog expressed in neurons (N-WASP), were found to possess short peptide motifs homologous to one part of verprolin. However, the physiological function of the homologous regions (verprolin-homology domain, VPH domain) remains unknown. Here we report the importance of the VPH domain as the direct actin binding region. In the case of N-WASP, the VPH domain co-acts with the cofilinhomologous region to sever actin filaments in vitro. Furthermore, the VPH domain is indispensable for the reorganization of the actin cytoskeleton by N-WASP downstream of tyrosine kinases in living cells. All data demonstrate that the VPH domain plays critical roles in the regulation of the actin cytoskeleton.

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Cytoskeleton / metabolism*
  • Fungal Proteins / genetics*
  • Microfilament Proteins / genetics*
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Wiskott-Aldrich Syndrome / genetics
  • Wiskott-Aldrich Syndrome / metabolism
  • Wiskott-Aldrich Syndrome Protein, Neuronal


  • Actins
  • Fungal Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • VRP1 protein, S cerevisiae
  • Wiskott-Aldrich Syndrome Protein, Neuronal