Insulin stimulates syntaxin4 SNARE complex assembly via a novel regulatory mechanism

Dimitrios Kioumourtzoglou, Gwyn W. Gould, Nia J. Bryant

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Insulin stimulates glucose transport into fat and muscle cells by increasing the exocytic trafficking rate of the GLUT4 facilitative glucose transporter from intracellular stores to the plasma membrane. Delivery of GLUT4 to the plasma membrane is mediated by formation of functional SNARE complexes containing syntaxin4, SNAP23, and VAMP2. Here we have used an in situ proximity ligation assay to integrate these two observations by demonstrating for the first time that insulin stimulation causes an increase in syntaxin4-containing SNARE complex formation in adipocytes. Furthermore, we demonstrate that insulin brings about this increase in SNARE complex formation by mobilizing a pool of syntaxin4 held in an inactive state under basal conditions. Finally, we have identified phosphorylation of the regulatory protein Munc18c, a direct target of the insulin receptor, as a molecular switch to coordinate this process. Hence, this report provides molecular detail of how the cell alters membrane traffic in response to an external stimulus, in this case, insulin.

Original languageEnglish
Pages (from-to)1271-1279
Number of pages9
JournalMolecular and Cellular Biology
Volume34
Issue number7
Early online date27 Jan 2014
DOIs
Publication statusPublished - 30 Apr 2014

Keywords

  • GLUT4
  • glucose transporter
  • intracellular stores
  • plasma membrane

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