The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly.
Although small GTP-binding proteins of the Rho family have been implicated in signaling to the actin cytoskeleton, the exact nature of the linkage has remained obscure. We describe a novel mechanism that links one Rho family member, Cdc42, to actin polymerization. N-WASP, a ubiquitously expressed Cdc42-interacting protein, is required for Cdc42-stimulated actin polymerization in Xenopus egg extracts. The C terminus of N-WASP binds to the Arp2/3 complex and dramatically stimulates its ability to nucleate actin polymerization. Although full-length N-WASP is less effective, its activity can be greatly enhanced by Cdc42 and phosphatidylinositol (4,5) bisphosphate. Therefore, N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization.
Rohatgi
R
R
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ma
L
L
Miki
H
H
Lopez
M
M
Kirchhausen
T
T
Takenawa
T
T
Kirschner
M W
MW
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001704:Biopolymers / Q000378:metabolism; D002417:Cattle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D014981:Xenopus; D020764:cdc42 GTP-Binding Protein
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D001704:Biopolymers; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D019269:Phosphatidylinositol 4,5-Diphosphate; D011994:Recombinant Proteins; C495770:Wasl protein, rat; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein