Author: ["Natasha K. Hussain","Sarah Jenna","Michael Glogauer","Christopher C. Quinn","Sylwia Wasiak","Michel Guipponi","Stylianos E. Antonarakis","Brian K. Kay","Thomas P. Stossel","Nathalie Lamarche-Vane","Peter S. McPherson"]
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Abstract
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.Cite this article
Hussain, N., Jenna, S., Glogauer, M. et al. Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 3, 927–932 (2001). https://doi.org/10.1038/ncb1001-927 