WIP regulates N-WASP-mediated actin polymerization and filopodium formation.
Induction of filopodia is dependent on activation of the small GTPase Cdc42 and on neural Wiskott-Aldrich-syndrome protein (N-WASP). Here we show that WASP-interacting protein (WIP) interacts directly with N-WASP and actin. WIP retards N-WASP/Cdc42-activated actin polymerization mediated by the Arp2/3 complex, and stabilizes actin filaments. Microinjection of WIP into NIH ... 3T3 fibroblasts induces filopodia; this is inhibited by microinjection of anti-N-WASP antibody. Microinjection of anti-WIP antibody inhibits induction of filopodia by bradykinin, by an active Cdc42 mutant (Cdc42(V12)) and by N-WASP. Our results indicate that WIP and N-WASP may act as a functional unit in filopodium formation, which is consistent with their role in actin-tail formation in cells infected with vaccinia virus or Shigella.
Mesh Terms:
3T3 Cells, Actin-Related Protein 2, Actin-Related Protein 3, Actins, Animals, Blotting, Western, Bradykinin, Carrier Proteins, Cell Line, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Glutathione Transferase, Mice, Microscopy, Fluorescence, Mutation, Nerve Tissue Proteins, Protein Binding, Protein Structure, Tertiary, Pseudopodia, Rabbits, Recombinant Fusion Proteins, Recombinant Proteins, Shigella, Signal Transduction, Time Factors, Two-Hybrid System Techniques, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein
3T3 Cells, Actin-Related Protein 2, Actin-Related Protein 3, Actins, Animals, Blotting, Western, Bradykinin, Carrier Proteins, Cell Line, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Glutathione Transferase, Mice, Microscopy, Fluorescence, Mutation, Nerve Tissue Proteins, Protein Binding, Protein Structure, Tertiary, Pseudopodia, Rabbits, Recombinant Fusion Proteins, Recombinant Proteins, Shigella, Signal Transduction, Time Factors, Two-Hybrid System Techniques, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein
Nat. Cell Biol.
Date: May. 01, 2001
PubMed ID: 11331876
View in: Pubmed Google Scholar
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