Real-time trafficking and signaling of the glucagon-like peptide-1 receptor
| Autor: | Helle Iversen, Nikolaj Kulahin, Hans Bräuner-Osborne, Sarah Noerklit Roed, Karen Arevad Cappelen, Anna Secher, Janne Lehtonen, Jesper Mosolff Mathiesen, Lauge Schäffer, Christina Rye Underwood, Maria Waldhoer, Jacob Hecksher-Soerensen, Jennifer L. Whistler, Pernille Wismann, Sanne Moeller Knudsen |
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| Rok vydání: | 2014 |
| Předmět: |
endocrine system
Incretin Biology Incretins Time-Lapse Imaging Biochemistry Glucagon-Like Peptide-1 Receptor Islets of Langerhans Mice Endocrinology Glucagon-Like Peptide 1 Cyclic AMP Receptors Glucagon medicine Animals Humans Receptor Molecular Biology Glucagon-like peptide 1 receptor G protein-coupled receptor Protein Stability Venoms Liraglutide Pancreatic islets digestive oral and skin physiology HEK 293 cells Cell biology Mice Inbred C57BL Protein Transport HEK293 Cells medicine.anatomical_structure Proteolysis Exenatide Signal transduction Peptides hormones hormone substitutes and hormone antagonists Signal Transduction medicine.drug |
| Zdroj: | Molecular and Cellular Endocrinology. 382:938-949 |
| ISSN: | 0303-7207 |
| Popis: | The glucagon-like peptide-1 incretin receptor (GLP-1R) of family B G protein-coupled receptors (GPCRs) is a major drug target in type-2-diabetes due to its regulatory effect on post-prandial blood-glucose levels. The mechanism(s) controlling GLP-1R mediated signaling are far from fully understood. A fundamental mechanism controlling the signaling capacity of GPCRs is the post-endocytic trafficking of receptors between recycling and degradative fates. Here, we combined microscopy with novel real-time assays to monitor both receptor trafficking and signaling in living cells. We find that the human GLP-1R internalizes rapidly and with similar kinetics in response to equipotent concentrations of GLP-1 and the stable GLP-1 analogues exendin-4 and liraglutide. Receptor internalization was confirmed in mouse pancreatic islets. GLP-1R is shown to be a recycling receptor with faster recycling rates mediated by GLP-1 as compared to exendin-4 and liraglutide. Furthermore, a prolonged cycling of ligand-activated GLP-1Rs was observed and is suggested to be correlated with a prolonged cAMP signal. |
| Databáze: | OpenAIRE |
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