The Toca-1-N-WASP Complex Links Filopodial Formation to Endocytosis
Copyright policy )The Toca-1-N-WASP Complex Links Filopodial Formation to Endocytosis
The transducer of Cdc42-dependent actin assembly (Toca-1)-N-WASP complex was isolated as an essential cofactor for Cdc42-driven actin polymerization in vitro. Toca-1 consists of an N-terminal F-BAR domain, followed by a Cdc42 binding site (HR1 domain) and an SH3 domain, (the N-WASP interacting site). N-WASP is an activator of actin nucleation through the Arp2/3 complex. The aim of the present study was to investigate the cellular function of the Toca-1-N-WASP complex. We report that Toca-1 induces filopodia and neurites as does N-WASP in N1E115 neuroblastoma cells. Toca-1 requires the F-BAR domain, Cdc42 binding site, and SH3 domain to induce filopodia. Toca-1 and N-WASP both require each other to induce filopodia. The expression of Toca-1 and N-WASP affects the distribution, size, and number of Rab5 positive membranes. Toca-1 interacts directly with N-WASP in filopodia and Rab5 membrane as seen by Forster resonance energy transfer. Thus the Toca-1-N-WASP complex localizes to and induces the formation of filopodia and endocytic vesicles. Last, three inhibitors of endocytosis, Dynamin-K44A, Eps15Delta95/295, and clathrin heavy chain RNA interference, block Toca-1-induced filopodial formation. Taken together, these data suggest that the Toca-1-N-WASP complex can link filopodial formation to endocytosis.
- Institute of Medical Biology Singapore
Binding Sites, Wiskott-Aldrich Syndrome Protein, Neuronal, Endocytosis, src Homology Domains, Microscopy, Fluorescence, Cell Line, Tumor, Fluorescence Resonance Energy Transfer, Mutagenesis, Site-Directed, Neurites, Humans, RNA Interference, Pseudopodia, Carrier Proteins, cdc42 GTP-Binding Protein, rab5 GTP-Binding Proteins
Binding Sites, Wiskott-Aldrich Syndrome Protein, Neuronal, Endocytosis, src Homology Domains, Microscopy, Fluorescence, Cell Line, Tumor, Fluorescence Resonance Energy Transfer, Mutagenesis, Site-Directed, Neurites, Humans, RNA Interference, Pseudopodia, Carrier Proteins, cdc42 GTP-Binding Protein, rab5 GTP-Binding Proteins
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