Negative Regulation of Fibroblast Motility by Ena/VASP Proteins

Cell. 2000 Jun 23;101(7):717-28. doi: 10.1016/s0092-8674(00)80884-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / physiology*
  • Cell Movement / physiology*
  • DNA-Binding Proteins / physiology*
  • Fibroblasts / cytology*
  • Fibroblasts / physiology*
  • Gene Expression
  • Gene Expression Regulation / physiology
  • Listeria monocytogenes
  • Microfilament Proteins / physiology
  • Phosphoproteins / physiology*

Substances

  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • ENA-VASP proteins
  • Microfilament Proteins
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein