A dual role for IQGAP1 in regulating exocytosis

Eric N. Rittmeyer, Samira Daniel, Shu Chan Hsu, Mahasin A. Osman

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Polarized secretion is a tightly regulated event generated by conserved, asymmetrically localized multiprotein complexes, and the mechanism(s) underlying its temporal and spatial regulation are only beginning to emerge. Although yeast Iqg1p has been identified as a positional marker linking polarity and exocytosis cues, studies on its mammalian counterpart, IQGAP1, have focused on its role in organizing cytoskeletal architecture, for which the underlying mechanism is unclear. Here, we report that IQGAP1 associates and co-localizes with the exocyst-septin complex, and influences the localization of the exocyst and the organization of septin. We further show that activation of CDC42 GTPase abolishes this association and inhibits secretion in pancreatic β-cells. Whereas the N-terminus of IQGAP1 binds the exocyst-septin complex, enhances secretion and abrogates the inhibition caused by CDC42 or the depletion of IQGAP1, the C-terminus, which binds CDC42, inhibits secretion. Pulse-chase experiments indicate that IQGAP1 influences protein-synthesis rates, thus regulating exocytosis. We propose and discuss a model in which IQGAP1 serves as a conformational switch to regulate exocytosis.

Original languageEnglish (US)
Pages (from-to)391-403
Number of pages13
JournalJournal of cell science
Volume121
Issue number3
DOIs
StatePublished - Feb 1 2008

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Cell polarity
  • IQGAP1
  • Insulin secretion

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