Insulin stimulates syntaxin4 SNARE complex assembly via a novel regulatory mechanism

Kioumourtzoglou, D., Gould, G. W. and Bryant, N. J. (2014) Insulin stimulates syntaxin4 SNARE complex assembly via a novel regulatory mechanism. Molecular and Cellular Biology, 34(7), pp. 1271-1279. (doi:10.1128/MCB.01203-13)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Gould, Professor Gwyn and Bryant, Dr Nia and Kioumourtzoglou, Mr Dimitrios
Authors: Kioumourtzoglou, D., Gould, G. W., and Bryant, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Molecular and Cellular Biology
Publisher:American Society for Microbiology
ISSN (Online):1098-5549

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
580731How does tyrosine phosphorylation of SNARE proteins control GLUT4 vesicle fusion with the plasma membrane?Gwyn GouldDiabetes UK (DIABETESUK)11/0004289RI MOLECULAR CELL & SYSTEMS BIOLOGY