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

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

Author information

1
Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.

Abstract

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.

PMID:
18923426
PMCID:
PMC2585163
DOI:
10.1038/emboj.2008.211
[Indexed for MEDLINE]
Free PMC Article

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