Interaction of Munc18 and Syntaxin in the regulation of insulin secretion
- Joint Laboratory of the Institute of Biophysics and Huazhong University of Science and Technology, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)
- National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)
Syntaxin1A and Munc18-1 play essential roles in exocytosis. However, the molecular mechanism and the functional roles of their interaction in insulin secretion remain to be explored. Using membrane capacitance measurement, we examine effect of overexpressing Munc18-1 on exocytosis in pancreatic {beta} cells. The results show that Munc18-1 negatively regulates vesicle fusion. To probe the interaction between Munc18-1 and Syntaxin1A, Munc18-1-Tdimer2 and EGFP-Syntaxin1A were co-transfected into INS-1 cells. FRET measurement confirmed that Munc18-1 interacted with wild type Syntaxin 1A, but not the constitutively open form (DM) of Syntaxin1A. Overexpressing DM in primary pancreatic {beta} cells augmented insulin secretion, and this effect can overcome the inhibitory effect of Munc18-1 overexpression. We propose that Munc18-1 inhibitis the SNARE complex assembly by stabilizing Syntaxin1A in a closed conformation in vesicle priming process, therefore negatively regulates insulin secretion.
- OSTI ID:
- 20991511
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 360, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.06.107; PII: S0006-291X(07)01338-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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