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

Barg, Sebastian LU ; Huang, P; Eliasson, Lena LU ; 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
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
ISSN
0021-9533
language
English
LU publication?
yes
id
c0e80266-2b9f-481c-be48-1e3526321981 (old id 1119803)
date added to LUP
2008-06-24 12:31:29
date last changed
2018-05-29 10:37:59
@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},
  keyword      = {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},
}