Abstract
Lamellipodial protrusion is regulated by Ena/VASP proteins. We identified Lamellipodin (Lpd) as an Ena/VASP binding protein. Both proteins colocalize at the tips of lamellipodia and filopodia. Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility. Lpd contains a PH domain that binds specifically to PI(3,4)P2, an asymmetrically localized signal in chemotactic cells. Lpd's PH domain can localize to ruffles in PDGF-treated fibroblasts. Lpd overexpression increases lamellipodial protrusion velocity, an effect observed when Ena/VASP proteins are overexpressed or artificially targeted to the plasma membrane. Conversely, knockdown of Lpd expression impairs lamellipodia formation, reduces velocity of residual lamellipodial protrusion, and decreases F-actin content. These phenotypes are more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors of the actin cytoskeleton in addition to Ena/VASP.
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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Actins / metabolism
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Amino Acid Sequence
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Adhesion Molecules / chemistry*
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Line
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Cerebral Cortex / cytology
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Fibroblasts / drug effects
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Focal Adhesions / metabolism
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Gene Expression Regulation
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Glutathione Transferase / metabolism
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HeLa Cells
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Humans
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Kinetics
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Lentivirus / genetics
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Ligands
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Membrane Proteins
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Microfilament Proteins
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Molecular Sequence Data
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Neurons / chemistry
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Phosphoproteins / chemistry*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Platelet-Derived Growth Factor / pharmacology
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary
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Pseudopodia / drug effects
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Pseudopodia / metabolism*
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RNA, Small Interfering / metabolism
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Vaccinia / metabolism
Substances
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Actins
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Carrier Proteins
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Cell Adhesion Molecules
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Evl protein, mouse
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Ligands
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Membrane Proteins
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Microfilament Proteins
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Phosphoproteins
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Platelet-Derived Growth Factor
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Protein Isoforms
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RAPH1 protein, human
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RNA, Small Interfering
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Recombinant Fusion Proteins
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vasodilator-stimulated phosphoprotein
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Glutathione Transferase