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Scientific article
English

Munc 18-1 and granuphilin collaborate during insulin granule exocytosis

Contributors

Tomas Catala, Alejandra Del Don; Meda, Paolo; Regazzi, Romano; Pessin, Jeffrey E.; Halban, Philippe A.

Published in

Traffic, vol. 9, no. 5, p. 813-832

Publication date

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.

Keywords

  • Animals
  • Anti-Bacterial Agents/metabolism
  • Autophagy
  • Cell Line
  • Doxycycline/metabolism
  • Exocytosis/physiology
  • Glucose/metabolism
  • Humans
  • Insulin/metabolism
  • Insulin-Secreting Cells/cytology/metabolism
  • Munc18 Proteins/genetics/metabolism
  • RNA Interference
  • Rats
  • Secretory Vesicles/chemistry/metabolism
  • Synaptosomal-Associated Protein 25/metabolism
  • Syntaxin 1/metabolism
  • Vacuoles/metabolism
  • Vesicle-Associated Membrane Protein 2/metabolism
  • Vesicular Transport Proteins/genetics/metabolism

UNIGE affiliation entities

Not a UNIGE publication

Citation (ISO format)

TOMAS CATALA, Alejandra Del Don et al. Munc 18-1 and granuphilin collaborate during insulin granule exocytosis. In: Traffic, 2008, vol. 9, n° 5, p. 813–832. doi: 10.1111/j.1600-0854.2008.00709.x

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

1398-9219
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Technical informations

Creation

17/02/2009 13:55:00

First validation

17/02/2009 13:55:00

Update

14/03/2023 15:00:40

Status update

14/03/2023 15:00:40

Last indexation

29/10/2024 11:10:01
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