Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1119803
- author
- Barg, Sebastian LU ; Huang, P ; Eliasson, Lena LU ; Nelson, D J ; Obermüller, Stefanie LU ; Rorsman, Patrik LU ; Thevenod, F and Renström, Erik LU
- organization
- publishing date
- 2001
- 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}}, }