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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / metabolism*
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Actin Cytoskeleton / ultrastructure
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Actin Depolymerizing Factors
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Actins / metabolism
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Animals
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Cell Adhesion Molecules / metabolism*
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Cell Compartmentation / physiology
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Cell Movement / physiology*
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Cell Size / physiology
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Cells, Cultured
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DNA-Binding Proteins / metabolism*
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Destrin
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Microfilament Proteins / metabolism*
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Microspheres
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Phosphoproteins / metabolism*
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Polymers / metabolism
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Protein Transport / physiology
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Pseudopodia / metabolism*
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Pseudopodia / ultrastructure
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Rats
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Vasodilator-Stimulated Phosphoprotein
Substances
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Actin Depolymerizing Factors
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Actins
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Cell Adhesion Molecules
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DNA-Binding Proteins
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Destrin
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ENA-VASP proteins
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Microfilament Proteins
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Phosphoproteins
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Polymers
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Vasodilator-Stimulated Phosphoprotein