Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP

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

Research output: Contribution to journalArticlepeer-review

290 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)927-932
Number of pages6
JournalNature cell biology
Volume3
Issue number10
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Cell Biology

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