@article{a785ade147d346f8853e314f1ee286e4,
title = "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP",
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 domains1,3-7. 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.",
author = "Hussain, {Natasha K.} and Sarah Jenna and Michael Glogauer and Quinn, {Christopher C.} and Sylwia Wasiak and Michel Guipponi and Antonarakis, {Stylianos E.} and Kay, {Brian K.} and Stossel, {Thomas P.} and Nathalie Lamarche-Vane and McPherson, {Peter S.}",
note = "Funding Information: ACKNOWLEDGMENTS We would like to thank H. Miki, and M. Olson for important reagents used in this study. We also thank J. Bergeron and D. A. Schafer for discussion and J. Presley for assistance with confocal microscopy. This research was supported by Canadian Institutes of Health Research (CIHR) grants to P.S.M. and N.L.-V., and by a National Cancer Institute of Canada Grant to N.L.-V. P.S.M. and N.L.-V. acknowledge support from the Canadian Foundation for Innovation. T.P.S. is supported by a USPHS grant and by the Edwin S. Webster Foundation. C.C.Q. is supported by a NINDS grant to S. Hockfield of Yale University. N.K.H. and S.W. are supported by studentships from the Fonds De La Recherche En Sant{\'e} Du Qu{\'e}bec and the Natural Sciences and Engineering Research Council, respectively. S.J. is a CIHR postdoctoral fellow. N.L.-V. is a Junior Scholar of the Fonds De La Recherche En Sant{\'e} Du Qu{\'e}bec. P.S.M. is a CIHR Investigator. Correspondence and requests for materials should be addressed to P.S.M.",
year = "2001",
doi = "10.1038/ncb1001-927",
language = "English (US)",
volume = "3",
pages = "927--932",
journal = "Nature cell biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "10",
}