Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics.
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.
Mesh Terms:
Actins, Amino Acid Sequence, Binding Sites, Carrier Proteins, Cell Adhesion Molecules, Cell Line, Cerebral Cortex, Fibroblasts, Focal Adhesions, Gene Expression Regulation, Glutathione Transferase, Hela Cells, Humans, Kinetics, Lentivirus, Ligands, Membrane Proteins, Microfilament Proteins, Molecular Sequence Data, Neurons, Phosphoproteins, Platelet-Derived Growth Factor, Protein Isoforms, Protein Structure, Tertiary, Pseudopodia, RNA, Small Interfering, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Vaccinia
Actins, Amino Acid Sequence, Binding Sites, Carrier Proteins, Cell Adhesion Molecules, Cell Line, Cerebral Cortex, Fibroblasts, Focal Adhesions, Gene Expression Regulation, Glutathione Transferase, Hela Cells, Humans, Kinetics, Lentivirus, Ligands, Membrane Proteins, Microfilament Proteins, Molecular Sequence Data, Neurons, Phosphoproteins, Platelet-Derived Growth Factor, Protein Isoforms, Protein Structure, Tertiary, Pseudopodia, RNA, Small Interfering, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Vaccinia
Dev. Cell
Date: Oct. 01, 2004
PubMed ID: 15469845
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