Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP.
Intersectin-s is a modular scaffolding protein regulating the formation of clathrin-coated vesicles. In addition to the Eps15 homology (EH) and Src homology 3 (SH3) domains of intersectin-s, the neuronal variant (intersectin-l) also has Dbl homology (DH), pleckstrin homology (PH) and C2 domains. We now show that intersectin-l functions through its ... DH domain as a guanine nucleotide exchange factor (GEF) for Cdc42. In cultured cells, expression of DH-domain-containing constructs cause actin rearrangements specific for Cdc42 activation. Moreover, in vivo studies reveal that stimulation of Cdc42 by intersectin-l accelerates actin assembly via N-WASP and the Arp2/3 complex. N-WASP binds directly to intersectin-l and upregulates its GEF activity, thereby generating GTP-bound Cdc42, a critical activator of N-WASP. These studies reveal a role for intersectin-l in a novel mechanism of N-WASP activation and in regulation of the actin cytoskeleton.
Mesh Terms:
Actins, Adaptor Proteins, Vesicular Transport, Animals, Carrier Proteins, Cell Line, Genes, Reporter, Humans, Microscopy, Confocal, Models, Biological, Nerve Tissue Proteins, Neutrophils, Phalloidine, Protein Structure, Tertiary, Recombinant Fusion Proteins, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein
Actins, Adaptor Proteins, Vesicular Transport, Animals, Carrier Proteins, Cell Line, Genes, Reporter, Humans, Microscopy, Confocal, Models, Biological, Nerve Tissue Proteins, Neutrophils, Phalloidine, Protein Structure, Tertiary, Recombinant Fusion Proteins, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein
Nat. Cell Biol.
Date: Oct. 01, 2001
PubMed ID: 11584276
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