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

Nat Cell Biol. 2001 Oct;3(10):927-32. doi: 10.1038/ncb1001-927.


Intersectin-s is a modular scaffolding protein regulating the formation of clathrin-coated vesicles. 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 domains. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Adaptor Proteins, Vesicular Transport*
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • Genes, Reporter / genetics
  • Humans
  • Microscopy, Confocal
  • Models, Biological
  • Nerve Tissue Proteins / metabolism*
  • Neutrophils / metabolism
  • Phalloidine / metabolism
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • cdc42 GTP-Binding Protein / metabolism*


  • Actins
  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • WASL protein, human
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • intersectin 1
  • Phalloidine
  • cdc42 GTP-Binding Protein