The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility

Traffic. 2010 Jun;11(6):782-99. doi: 10.1111/j.1600-0854.2010.01062.x. Epub 2010 Mar 17.

Abstract

In migrating cells, the cytoskeleton coordinates signal transduction and redistribution of transmembrane proteins, including integrins and growth factor receptors. Supervillin is an F-actin- and myosin II-binding protein that tightly associates with signaling proteins in cholesterol-rich, 'lipid raft' membrane microdomains. We show here that supervillin also can localize with markers for early and sorting endosomes (EE/SE) and with overexpressed components of the Arf6 recycling pathway in the cell periphery. Supervillin tagged with the photoswitchable fluorescent protein, tdEos, moves both into and away from dynamic structures resembling podosomes at the basal cell surface. Rapid integrin recycling from EE/SE is inhibited in supervillin-knockdown cells, but the rates of integrin endocytosis and recycling from the perinuclear recycling center (PNRC) are unchanged. A lack of synergy between supervillin knockdown and the actin filament barbed-end inhibitor, cytochalasin D, suggests that both treatments affect actin-dependent rapid recycling. Supervillin also enhances signaling from the epidermal growth factor receptor (EGFR) to extracellular signal-regulated kinases (ERKs) 1 and 2 and increases the velocity of cell translocation. These results suggest that supervillin, F-actin and associated proteins coordinate a rapid, basolateral membrane recycling pathway that contributes to ERK signaling and actin-based cell motility.

Publication types

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

MeSH terms

  • Actins / chemistry*
  • Animals
  • COS Cells
  • Cell Movement*
  • Chlorocebus aethiops
  • Cytochalasin D / chemistry
  • Endocytosis
  • Endosomes / metabolism
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • HeLa Cells
  • Humans
  • Integrins / metabolism*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / physiology
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / physiology
  • Signal Transduction

Substances

  • Actins
  • Integrins
  • Membrane Proteins
  • Microfilament Proteins
  • SVIL protein, human
  • Cytochalasin D
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases