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

Cheviet, Severine ; Bezzi, Paola ; Ivarsson, Rosita LU ; Renström, Erik LU ; Viertl, David ; Kasas, Sandor ; Catsicas, Stefan and Regazzi, Romano (2006) In Journal of Cell Science 119(14). p.2912-2920
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
exocytosis, SNARE, insulin, TIRF
in
Journal of Cell Science
volume
119
issue
14
pages
2912 - 2920
publisher
The Company of Biologists Ltd
external identifiers
  • wos:000238840300009
  • scopus:33746853822
ISSN
0021-9533
DOI
10.1242/jcs.03037
language
English
LU publication?
yes
id
fc7890dc-0f2c-49c7-b98c-3f65ebc7957f (old id 404115)
date added to LUP
2016-04-01 12:30:09
date last changed
2021-06-08 01:16:10
@article{fc7890dc-0f2c-49c7-b98c-3f65ebc7957f,
  abstract     = {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.},
  author       = {Cheviet, Severine and Bezzi, Paola and Ivarsson, Rosita and Renström, Erik and Viertl, David and Kasas, Sandor and Catsicas, Stefan and Regazzi, Romano},
  issn         = {0021-9533},
  language     = {eng},
  number       = {14},
  pages        = {2912--2920},
  publisher    = {The Company of Biologists Ltd},
  series       = {Journal of Cell Science},
  title        = {Tomosyn-1 is involved in a post-docking event required for pancreatic beta-cell exocytosis},
  url          = {http://dx.doi.org/10.1242/jcs.03037},
  doi          = {10.1242/jcs.03037},
  volume       = {119},
  year         = {2006},
}