VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for Ca(2+)-but not for GTP gamma S-induced insulin secretion.

Détails

ID Serval
serval:BIB_EC20208E67A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for Ca(2+)-but not for GTP gamma S-induced insulin secretion.
Périodique
EMBO Journal
Auteur⸱e⸱s
Regazzi R., Wollheim C.B., Lang J., Theler J.M., Rossetto O., Montecucco C., Sadoul K., Weller U., Palmer M., Thorens B.
ISSN
0261-4189[print], 0261-4189[linking]
Statut éditorial
Publié
Date de publication
06/1995
Volume
14
Numéro
12
Pages
2723-2730
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
VAMP proteins are important components of the machinery controlling docking and/or fusion of secretory vesicles with their target membrane. We investigated the expression of VAMP proteins in pancreatic beta-cells and their implication in the exocytosis of insulin. cDNA cloning revealed that VAMP-2 and cellubrevin, but not VAMP-1, are expressed in rat pancreatic islets and that their sequence is identical to that isolated from rat brain. Pancreatic beta-cells contain secretory granules that store and secrete insulin as well as synaptic-like microvesicles carrying gamma-aminobutyric acid. After subcellular fractionation on continuous sucrose gradients, VAMP-2 and cellubrevin were found to be associated with both types of secretory vesicle. The association of VAMP-2 with insulin-containing granules was confirmed by confocal microscopy of primary cultures of rat pancreatic beta-cells. Pretreatment of streptolysin-O permeabilized insulin-secreting cells with tetanus and botulinum B neurotoxins selectively cleaved VAMP-2 and cellubrevin and abolished Ca(2+)-induced insulin release (IC50 approximately 15 nM). By contrast, the pretreatment with tetanus and botulinum B neurotoxins did not prevent GTP gamma S-stimulated insulin secretion. Taken together, our results show that pancreatic beta-cells express VAMP-2 and cellubrevin and that one or both of these proteins selectively control Ca(2+)-mediated insulin secretion.
Mots-clé
Animals, Botulinum Toxins/pharmacology, Brain Chemistry, Calcium/pharmacology, Cell Fractionation, Cell Line, Cloning, Molecular, Cytoplasmic Granules/metabolism, Exocytosis/drug effects, Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology, Insulin/analysis, Insulin/secretion, Islets of Langerhans/chemistry, Islets of Langerhans/metabolism, Membrane Proteins/analysis, Membrane Proteins/biosynthesis, Nerve Tissue Proteins/analysis, Nerve Tissue Proteins/biosynthesis, R-SNARE Proteins, Rats, Sequence Analysis, DNA, Tetanus Toxin/pharmacology, Vesicle-Associated Membrane Protein 3
Pubmed
Web of science
Création de la notice
24/01/2008 14:30
Dernière modification de la notice
20/08/2019 16:14
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