Negative regulation of fibroblast motility by Ena/VASP proteins.
Ena/VASP proteins have been implicated in cell motility through regulation of the actin cytoskeleton and are found at focal adhesions and the leading edge. Using overexpression, loss-of-function, and inhibitory approaches, we find that Ena/VASP proteins negatively regulate fibroblast motility. A dose-dependent decrease in movement is observed when Ena/VASP proteins are overexpressed in fibroblasts. Neutralization or deletion of all Ena/VASP proteins results in increased cell movement. Selective depletion of Ena/VASP proteins from focal adhesions, but not the leading edge, has no effect on motility. Constitutive membrane targeting of Ena/VASP proteins inhibits motility. These results are in marked contrast to current models for Ena/VASP function derived mainly from their role in the actin-driven movement of Listeria monocytogenes.
Bear
J E
JE
Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.
Loureiro
J J
JJ
Libova
I
I
Fässler
R
R
Wehland
J
J
Gertler
F B
FB
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology; D008089:Listeria monocytogenes; D008840:Microfilament Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology*; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein