Article
- The EMBO Journal (2008) 27, 2943 - 2954
- doi:10.1038/emboj.2008.211
Published online: 16 October 2008
Subject Category:
Clustering of VASP actively drives processive, WH2 domain-mediated actin filament elongation
Dennis Breitsprecher1,a, Antje K Kiesewetter1,a, Joern Linkner1, Claus Urbanke1, Guenter P Resch2,3, J Victor Small2 and Jan Faix1
- Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany
- Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria
- Research Institute of Molecular Pathology, Vienna, Austria
Correspondence to:
Jan Faix, Department of Biophysical Chemistry, Hannover Medical School, OE4350, Carl-Neuberg-Strasse 1, Hannover D-30623, Germany. Tel.: +49 511 532 2928; Fax: +49 511 532 5966; E-mail: faix@bpc.mh-hannover.de
aThese authors contributed equally to this work
Received 19 May 2008; Accepted 17 September 2008
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.
Keywords:
- actin assembly,
- capping protein,
- Ena/VASP proteins,
- processivity,
- TIRF microscopy
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