Abstract
Wiskott-Aldrich syndrome protein (WASP) and N-WASP have emerged as key proteins connecting signalling cascades to actin polymerization. Here we show that the amino-terminal WH1 domain, and not the polyproline-rich region, of N-WASP is responsible for its recruitment to sites of actin polymerization during Cdc42-independent, actin-based motility of vaccinia virus. Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex. We propose that the N-WASP-WIP complex has a pivotal function in integrating signalling cascades that lead to actin polymerization.
MeSH terms
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Actin Cytoskeleton / chemistry
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Actin Cytoskeleton / metabolism*
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Actins / metabolism*
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Adaptor Proteins, Signal Transducing
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Amino Acid Motifs
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Biopolymers / chemistry
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Biopolymers / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cytoskeletal Proteins
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Fluorescent Antibody Technique
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins
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Movement
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Mutation / genetics
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism
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Phosphorylation
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Phosphotyrosine / metabolism
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Protein Binding
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Shigella / physiology
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Signal Transduction*
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Vaccinia virus / physiology
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Wiskott-Aldrich Syndrome / genetics
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Wiskott-Aldrich Syndrome Protein, Neuronal
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism
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src Homology Domains
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Biopolymers
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Carrier Proteins
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Cytoskeletal Proteins
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Intracellular Signaling Peptides and Proteins
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Nck protein
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Nerve Tissue Proteins
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Oncogene Proteins
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Recombinant Fusion Proteins
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WASL protein, human
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WIPF1 protein, human
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Wiskott-Aldrich Syndrome Protein, Neuronal
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Phosphotyrosine
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cdc42 GTP-Binding Protein