CRMP-1 enhances EVL-mediated actin elongation to build lamellipodia and the actin cortex

J Cell Biol. 2017 Aug 7;216(8):2463-2479. doi: 10.1083/jcb.201606084. Epub 2017 Jun 19.

Abstract

Cells can control actin polymerization by nucleating new filaments or elongating existing ones. We recently identified CRMP-1 as a factor that stimulates the formation of Listeria monocytogenes actin comet tails, thereby implicating it in actin assembly. We now show that CRMP-1 is a major contributor to actin assembly in epithelial cells, where it works with the Ena/VASP family member EVL to assemble the actin cytoskeleton in the apical cortex and in protruding lamellipodia. CRMP-1 and EVL bind to one another and together accelerate actin filament barbed-end elongation. CRMP-1 also stimulates actin assembly in the presence of VASP and Mena in vitro, but CRMP-1-dependent actin assembly in MDCK cells is EVL specific. Our results identify CRMP-1 as a novel regulator of actin filament elongation and reveal a surprisingly important role for CRMP-1, EVL, and actin polymerization in maintaining the structural integrity of epithelial sheets.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism*
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Movement*
  • Dogs
  • Epithelial Cells / metabolism*
  • Madin Darby Canine Kidney Cells
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Multimerization
  • Pseudopodia / metabolism*
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Time-Lapse Imaging
  • Transfection
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • CRMP1 protein, human
  • Cell Adhesion Molecules
  • EVL protein, human
  • Enah protein, human
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Wasf2 protein, mouse
  • Wiskott-Aldrich Syndrome Protein Family
  • vasodilator-stimulated phosphoprotein