Transglutaminase 2 transamidation activity during first-phase insulin secretion: natural substrates in INS-1E.

Détails

ID Serval
serval:BIB_EDF15E2EF682
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Transglutaminase 2 transamidation activity during first-phase insulin secretion: natural substrates in INS-1E.
Périodique
Acta Diabetologica
Auteur(s)
Russo L., Marsella C., Nardo G., Massignan T., Alessio M., Piermarini E., La Rosa S., Finzi G., Bonetto V., Bertuzzi F., Maechler P., Massa O.
ISSN
1432-5233 (Electronic)
ISSN-L
0940-5429
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
50
Numéro
1
Pages
61-72
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent transamidating and G protein activity. Previously, we reported that tgm2 -/- mice have an impaired insulin secretion and that naturally occurring TG2 mutations associated with familial, early-onset type 2 diabetes, show a defective transamidating activity. Aim of this study was to get a better insight into the role of TG2 in insulin secretion by identifying substrates of TG2 transamidating activity in the pancreatic beta cell line INS-1E. To this end, we labeled INS-1E that are capable of secreting insulin upon glucose stimulation in the physiologic range, with an artificial acyl acceptor (biotinamido-pentylamine) or donor (biotinylated peptide), in basal condition and after stimulus with glucose for 2, 5, and 8 min. Biotinylated proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. In addition, subcellular localization of TG2 in human endocrine pancreas was studied by electron microscopy. Among several TG2's transamidating substrates in INS-1E, mass spectrometry identified cytoplasmic actin (a result confirmed in human pancreatic islet), tropomyosin, and molecules that participate in insulin granule structure (e.g., GAPDH), glucose metabolism, or [Ca(2+)] sensing (e.g., calreticulin). Physical interaction between TG2 and cytoplasmic actin during glucose-stimulated first-phase insulin secretion was confirmed by co-immunoprecipitation. Electron microscopy revealed that TG2 is localized close to insulin and glucagon granules in human pancreatic islet. We propose that TG2's role in insulin secretion may involve cytoplasmic actin remodeling and may have a regulative action on other proteins during granule movement. A similar role of TG2 in glucagon secretion is also suggested.
Mots-clé
Animals, Cell Line, Tumor, GTP-Binding Proteins/chemistry, GTP-Binding Proteins/metabolism, Glucose/metabolism, Humans, Insulin/secretion, Insulin-Secreting Cells/chemistry, Insulin-Secreting Cells/secretion, Mass Spectrometry, Rats, Substrate Specificity, Transglutaminases/chemistry, Transglutaminases/metabolism
Pubmed
Web of science
Création de la notice
06/09/2016 13:08
Dernière modification de la notice
20/08/2019 16:15
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