The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility
Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology; Department of Cell Biology
Medical Subject Headings
Actins; Animals; COS Cells; *Cell Movement; Cercopithecus aethiops; Cytochalasin D; Endocytosis; Endosomes; Extracellular Signal-Regulated MAP Kinases; Hela Cells; Humans; Integrins; Membrane Proteins; Microfilament Proteins; Receptor, Epidermal Growth Factor; Signal Transduction
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.
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Citation: Traffic. 2010 Jun;11(6):782-99. Epub 2010 Mar 17. Link to article on publisher's site
Fang, Zhiyou; Takizawa, Norio; Wilson, Korey A.; Smith, Tara C.; Delprato, Anna M.; Davidson, Michael W.; Lambright, David G.; and Luna, Elizabeth J., "The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility" (2010). Luna Lab. 1.