A novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42.
We identified a novel adaptor protein that contains a Src homology (SH)3 domain, SH3 binding proline-rich sequences, and a leucine zipper-like motif and termed this protein WASP interacting SH3 protein (WISH). WISH is expressed predominantly in neural tissues and testis. It bound Ash/Grb2 through its proline-rich regions and neural Wiskott-Aldrich ... syndrome protein (N-WASP) through its SH3 domain. WISH strongly enhanced N-WASP-induced Arp2/3 complex activation independent of Cdc42 in vitro, resulting in rapid actin polymerization. Furthermore, coexpression of WISH and N-WASP induced marked formation of microspikes in Cos7 cells, even in the absence of stimuli. An N-WASP mutant (H208D) that cannot bind Cdc42 still induced microspike formation when coexpressed with WISH. We also examined the contribution of WISH to a rapid actin polymerization induced by brain extract in vitro. Arp2/3 complex was essential for brain extract-induced rapid actin polymerization. Addition of WISH to extracts increased actin polymerization as Cdc42 did. However, WISH unexpectedly could activate actin polymerization even in N-WASP-depleted extracts. These findings suggest that WISH activates Arp2/3 complex through N-WASP-dependent and -independent pathways without Cdc42, resulting in the rapid actin polymerization required for microspike formation.
Mesh Terms:
Actin-Related Protein 2, Actin-Related Protein 3, Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Blotting, Northern, Blotting, Western, Brain Chemistry, Carrier Proteins, Cattle, Cell Line, Cell Surface Extensions, Culture Media, Serum-Free, Cytoskeletal Proteins, GRB2 Adaptor Protein, Genes, Reporter, Humans, Leucine Zippers, Molecular Sequence Data, Muscle Proteins, Nerve Tissue Proteins, Polymers, Protein Binding, Proteins, Rats, Recombinant Fusion Proteins, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein, src Homology Domains
Actin-Related Protein 2, Actin-Related Protein 3, Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Blotting, Northern, Blotting, Western, Brain Chemistry, Carrier Proteins, Cattle, Cell Line, Cell Surface Extensions, Culture Media, Serum-Free, Cytoskeletal Proteins, GRB2 Adaptor Protein, Genes, Reporter, Humans, Leucine Zippers, Molecular Sequence Data, Muscle Proteins, Nerve Tissue Proteins, Polymers, Protein Binding, Proteins, Rats, Recombinant Fusion Proteins, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein, src Homology Domains
J. Cell Biol.
Date: Feb. 05, 2001
PubMed ID: 11157975
View in: Pubmed Google Scholar
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