Clustering of VASP actively drives processive, WH2 domain-mediated actin filament elongation

EMBO J. 2008 Nov 19;27(22):2943-54. doi: 10.1038/emboj.2008.211. Epub 2008 Oct 16.


Vasodilator-stimulated phosphoprotein (VASP) is a key regulator of dynamic actin structures like filopodia and lamellipodia, but its precise function in their formation is controversial. Using in vitro TIRF microscopy, we show for the first time that both human and Dictyostelium VASP are directly involved in accelerating filament elongation by delivering monomeric actin to the growing barbed end. In solution, DdVASP markedly accelerated actin filament elongation in a concentration-dependent manner but was inhibited by low concentrations of capping protein (CP). In striking contrast, VASP clustered on functionalized beads switched to processive filament elongation that became insensitive even to very high concentrations of CP. Supplemented with the in vivo analysis of VASP mutants and an EM structure of the protein, we propose a mechanism by which membrane-associated VASP oligomers use their WH2 domains to effect both the tethering of actin filaments and their processive elongation in sites of active actin assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Capping Proteins / metabolism
  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism*
  • Animals
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Dictyostelium / cytology
  • Dictyostelium / metabolism
  • Humans
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Microscopy, Fluorescence / methods
  • Models, Biological
  • Mutation
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Profilins / metabolism
  • Protein Structure, Tertiary
  • Protozoan Proteins / metabolism*


  • Actin Capping Proteins
  • Actins
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • Profilins
  • Protozoan Proteins
  • vasodilator-stimulated phosphoprotein