Antagonism Between Ena/VASP Proteins and Actin Filament Capping Regulates Fibroblast Motility

Cell. 2002 May 17;109(4):509-21. doi: 10.1016/s0092-8674(02)00731-6.

Abstract

Cell motility requires lamellipodial protrusion, a process driven by actin polymerization. Ena/VASP proteins accumulate in protruding lamellipodia and promote the rapid actin-driven motility of the pathogen Listeria. In contrast, Ena/VASP negatively regulate cell translocation. To resolve this paradox, we analyzed the function of Ena/VASP during lamellipodial protrusion. Ena/VASP-deficient lamellipodia protruded slower but more persistently, consistent with their increased cell translocation rates. Actin networks in Ena/VASP-deficient lamellipodia contained shorter, more highly branched filaments compared to controls. Lamellipodia with excess Ena/VASP contained longer, less branched filaments. In vitro, Ena/VASP promoted actin filament elongation by interacting with barbed ends, shielding them from capping protein. We conclude that Ena/VASP regulates cell motility by controlling the geometry of actin filament networks within lamellipodia.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Actin Depolymerizing Factors
  • Actins / metabolism
  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Cell Compartmentation / physiology
  • Cell Movement / physiology*
  • Cell Size / physiology
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Destrin
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Microfilament Proteins / metabolism*
  • Microspheres
  • Phosphoproteins / metabolism*
  • Polymers / metabolism
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Protein Transport / physiology
  • Pseudopodia / metabolism*
  • Pseudopodia / ultrastructure
  • Rats

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • Destrin
  • ENA-VASP proteins
  • Microfilament Proteins
  • Phosphoproteins
  • Polymers
  • vasodilator-stimulated phosphoprotein