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Tomosyn-1 is involved in a post-docking event required for pancreatic beta-cell exocytosis

På svenska

Author

  • Severine Cheviet
  • Paola Bezzi
  • Rosita Ivarsson
  • Erik Renström
  • David Viertl
  • Sandor Kasas
  • Stefan Catsicas
  • Romano Regazzi

Summary, in English

Although the assembly of a ternary complex between the SNARE proteins syntaxin-1, SNAP25 and VAMP2 is known to be crucial for insulin exocytosis, the mechanisms controlling this key event are poorly understood. We found that pancreatic beta-cells express different isoforms of tomosyn-1, a syntaxin-1-binding protein possessing a SNARE-like motif. Using atomic force microscopy we show that the SNARE-like domain of tomosyn-1 can form a complex with syntaxin-1 and SNAP25 but displays binding forces that are weaker than those observed for VAMP2 (237 +/- 13 versus 279 +/- 3 pN). In pancreatic beta-cells tomosyn-1 was found to be concentrated in cellular compartments enriched in insulin-containing secretory granules. Silencing of tomosyn-1 in the rat beta-cell line INS-1E by RNA interference did not affect the number of secretory granules docked at the plasma membrane but led to a reduction in stimulus-induced exocytosis. Replacement of endogenous tomosyn-1 with mouse tomosyn-1, which differs in the nucleotide sequence from its rat homologue and escapes silencing, restored a normal secretory rate. Taken together, our data suggest that tomosyn-1 is involved in a post-docking event that prepares secretory granules for fusion and is necessary to sustain exocytosis of pancreatic beta-cells in response to insulin secretagogues.

Publishing year

2006

Language

English

Pages

2912-2920

Publication/Series

Journal of Cell Science

Volume

119

Issue

14

Document type

Journal article

Publisher

The Company of Biologists Ltd

Topic

  • Endocrinology and Diabetes

Keywords

  • exocytosis
  • SNARE
  • insulin
  • TIRF

Status

Published

Research group

  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 0021-9533