Ena/VASP proteins cooperate with the WAVE complex to regulate the actin cytoskeleton

Dev Cell. 2014 Sep 8;30(5):569-84. doi: 10.1016/j.devcel.2014.08.001.

Abstract

Ena/VASP proteins and the WAVE regulatory complex (WRC) regulate cell motility by virtue of their ability to independently promote actin polymerization. We demonstrate that Ena/VASP and the WRC control actin polymerization in a cooperative manner through the interaction of the Ena/VASP EVH1 domain with an extended proline rich motif in Abi. This interaction increases cell migration and enables VASP to cooperatively enhance WRC stimulation of Arp2/3 complex-mediated actin assembly in vitro in the presence of Rac. Loss of this interaction in Drosophila macrophages results in defects in lamellipodia formation, cell spreading, and redistribution of Ena to the tips of filopodia-like extensions. Rescue experiments of abi mutants also reveals a physiological requirement for the Abi:Ena interaction in photoreceptor axon targeting and oogenesis. Our data demonstrate that the activities of Ena/VASP and the WRC are intimately linked to ensure optimal control of actin polymerization during cell migration and development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Amino Acid Sequence
  • Animals
  • Axons / physiology
  • Cell Line, Tumor
  • Cell Movement
  • DNA-Binding Proteins / metabolism*
  • Drosophila melanogaster
  • Gene Expression Regulation, Developmental*
  • Humans
  • Macrophages / metabolism
  • Molecular Sequence Data
  • Photoreceptor Cells, Invertebrate / metabolism
  • Proline / chemistry
  • Protein Structure, Tertiary
  • Pseudopodia / metabolism
  • Sequence Homology, Amino Acid
  • Wiskott-Aldrich Syndrome Protein Family / metabolism*

Substances

  • DNA-Binding Proteins
  • ENA-VASP proteins
  • Wiskott-Aldrich Syndrome Protein Family
  • Proline