A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization.
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.
Moreau
V
V
European Molecular Biology Laboratory, Heidelberg, Germany.
Frischknecht
F
F
Reckmann
I
I
Vincentelli
R
R
Rabut
G
G
Stewart
D
D
Way
M
M
D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009068:Movement; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012760:Shigella / Q000502:physiology; D015398:Signal Transduction; D014616:Vaccinia virus / Q000502:physiology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D001704:Biopolymers; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C078332:Nck protein; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; C495771:WASL protein, human; C109903:WIPF1 protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D019000:Phosphotyrosine; D020764:cdc42 GTP-Binding Protein