Brief Communication abstract
Nature Cell Biology 3, 927 - 932 (2001)
Published online: 12 September 2001 | doi:10.1038/ncb1001-927
Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP
Natasha K. Hussain1, Sarah Jenna2, Michael Glogauer3, Christopher C. Quinn4, Sylwia Wasiak1, Michel Guipponi5, Stylianos E. Antonarakis5, Brian K. Kay6, Thomas P. Stossel3, Nathalie Lamarche-Vane2 & Peter S. McPherson1,2
Intersectin-s is a modular scaffolding protein regulating the formation of clathrin-coated vesicles1, 2. 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 domains1, 3, 4, 5, 6, 7. 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.
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada
- Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A 2B2, Canada
- Hematology Division, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
- Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
- Division of Medical Genetics, University of Geneva Medical School, 1211 Geneva 4, Switzerland
- Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, USA
Correspondence to: Peter S. McPherson1,2 e-mail: peter.mcpherson@mcgill.ca
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REVIEWS RESEARCH |
