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 journalArticle

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
Externally publishedYes

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Actins
Guanine Nucleotide Exchange Factors
Proteins
Actin-Related Protein 2-3 Complex
Clathrin
src Homology Domains
Guanosine Triphosphate
Actin Cytoskeleton
intersectin 1
Cultured Cells
Up-Regulation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hussain, N. K., Jenna, S., Glogauer, M., Quinn, C. C., Wasiak, S., Guipponi, M., ... McPherson, P. S. (2001). Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nature Cell Biology, 3(10), 927-932. https://doi.org/10.1038/ncb1001-927

Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. / Hussain, Natasha K.; Jenna, Sarah; Glogauer, Michael; Quinn, Christopher C.; Wasiak, Sylwia; Guipponi, Michel; Antonarakis, Stylianos E.; Kay, Brian K.; Stossel, Thomas P.; Lamarche-Vane, Nathalie; McPherson, Peter S.

In: Nature Cell Biology, Vol. 3, No. 10, 2001, p. 927-932.

Research output: Contribution to journalArticle

Hussain, NK, Jenna, S, Glogauer, M, Quinn, CC, Wasiak, S, Guipponi, M, Antonarakis, SE, Kay, BK, Stossel, TP, Lamarche-Vane, N & McPherson, PS 2001, 'Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP', Nature Cell Biology, vol. 3, no. 10, pp. 927-932. https://doi.org/10.1038/ncb1001-927
Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M et al. Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nature Cell Biology. 2001;3(10):927-932. https://doi.org/10.1038/ncb1001-927
Hussain, Natasha K. ; Jenna, Sarah ; Glogauer, Michael ; Quinn, Christopher C. ; Wasiak, Sylwia ; Guipponi, Michel ; Antonarakis, Stylianos E. ; Kay, Brian K. ; Stossel, Thomas P. ; Lamarche-Vane, Nathalie ; McPherson, Peter S. / Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. In: Nature Cell Biology. 2001 ; Vol. 3, No. 10. pp. 927-932.
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