Journal article
Transglutaminase 2 transamidation activity during first-phase insulin secretion: natural substrates in INS-1E
Acta diabetologica, v 50(1), pp 61-72
01 Feb 2013
PMID: 22382775
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Transglutaminase 2 (TG2) is a multifunctional protein with Ca2+-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 [Ca2+] 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.
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Details
- Title
- Transglutaminase 2 transamidation activity during first-phase insulin secretion: natural substrates in INS-1E
- Creators
- Lucia Russo - Bambino Gesu Pediat Hosp, Res Inst, Lab Mendelian Diabet, I-00165 Rome, ItalyClaudia Marsella - Boston Children's HospitalGiovanni Nardo - Dulbecco Telethon InstituteTania Massignan - Mario Negri Institute for Pharmacological ResearchMassimo Alessio - San Raffaele University of RomeEmanuela Piermarini - Boston Children's HospitalStefano La Rosa - University of InsubriaGiovanna Finzi - University of InsubriaValentina Bonetto - Dulbecco Telethon InstituteFederico Bertuzzi - Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano NiguardaPierre Maechler - Geneva CollegeOrnella Massa - Boston Children's Hospital
- Publication Details
- Acta diabetologica, v 50(1), pp 61-72
- Publisher
- Springer Nature
- Number of pages
- 12
- Grant note
- Swiss National Science Foundation; Swiss National Science Foundation (SNSF) GGP09147 / Telethon; Fondazione Telethon
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000314033400008
- Scopus ID
- 2-s2.0-84873093284
- Other Identifier
- 991021900032204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Endocrinology & Metabolism