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Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification

Barg, Sebastian LU ; Huang, P ; Eliasson, Lena LU orcid ; Nelson, D J ; Obermüller, Stefanie LU ; Rorsman, Patrik LU ; Thevenod, F and Renström, Erik LU (2001) In Journal of Cell Science 114(Pt 11). p.2145-2154
Abstract
ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the... (More)
ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ClC-3 channels, Exocytosis, Sulfonylureas, Insulin, Granular pH
in
Journal of Cell Science
volume
114
issue
Pt 11
pages
2145 - 2154
publisher
The Company of Biologists Ltd
external identifiers
  • pmid:11493650
  • scopus:0034956026
ISSN
0021-9533
language
English
LU publication?
yes
id
c0e80266-2b9f-481c-be48-1e3526321981 (old id 1119803)
date added to LUP
2016-04-01 11:51:46
date last changed
2022-04-20 22:58:02
@article{c0e80266-2b9f-481c-be48-1e3526321981,
  abstract     = {{ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types.}},
  author       = {{Barg, Sebastian and Huang, P and Eliasson, Lena and Nelson, D J and Obermüller, Stefanie and Rorsman, Patrik and Thevenod, F and Renström, Erik}},
  issn         = {{0021-9533}},
  keywords     = {{ClC-3 channels; Exocytosis; Sulfonylureas; Insulin; Granular pH}},
  language     = {{eng}},
  number       = {{Pt 11}},
  pages        = {{2145--2154}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{Journal of Cell Science}},
  title        = {{Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification}},
  volume       = {{114}},
  year         = {{2001}},
}