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Munc 18-1 and Granuphilin Collaborate During Insulin Granule Exocytosis.
- Source :
- Traffic; May2008, Vol. 9 Issue 5, p813-832, 20p, 3 Color Photographs, 7 Graphs
- Publication Year :
- 2008
-
Abstract
- Munc 18-1 is a member of the Sec/Munc family of syntaxin-binding proteins known to bind to the plasma membrane Q-SNARE syntaxin1 and whose precise role in regulated exocytosis remains controversial. Here, we show that Munc 18-1 plays a positive role in regulated insulin secretion from pancreatic beta cells. Munc 18-1 depletion caused a loss in the secretory capacity of both transiently transfected INS 1E cells and a stable clone with tetracycline-regulated Munc 18-1 RNA interference. In addition, Munc 18-1-depleted cells exhibited defective docking of insulin granules to the plasma membrane and accumulated insulin in the trans Golgi network. Furthermore, glucose stimulation after Munc 18-1 depletion resulted in the rapid formation of autophagosomes. In contrast, overexpression of Munc 18-1 had no effect on insulin secretion. Although there was no detectable interaction between Munc 18-1 and Munc-18-interacting protein 1 or calcium/calmodulin-dependent serine protein kinase, Munc 18-1 associated with the granular protein granuphilin. This association was regulated by glucose and was required for the specific interaction of insulin granules with syntaxin1. We conclude that Munc 18-1 and granuphilin collaborate in the docking of insulin granules to the plasma membrane in an initial fusion-incompetent state, with Munc 18-1 subsequently playing a positive role in a later stage of insulin granule exocytosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- EXOCYTOSIS
INSULIN
PANCREATIC beta cells
TETRACYCLINE
RNA
Subjects
Details
- Language :
- English
- ISSN :
- 13989219
- Volume :
- 9
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Traffic
- Publication Type :
- Academic Journal
- Accession number :
- 31557880
- Full Text :
- https://doi.org/10.1111/j.1600-0854.2008.00709.x