The Journal of cell biology, 2017-12, Vol.216 (12), p.4153-4164
2017
Details
- Autor(en) / Beteiligte
- Titel
- cTAGE5 deletion in pancreatic β cells impairs proinsulin trafficking and insulin biogenesis in mice
- Ist Teil von
- The Journal of cell biology, 2017-12, Vol.216 (12), p.4153-4164
- Ort / Verlag
- United States: Rockefeller University Press
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Proinsulin is synthesized in the endoplasmic reticulum (ER) in pancreatic β cells and transported to the Golgi apparatus for proper processing and secretion into plasma. Defects in insulin biogenesis may cause diabetes. However, the underlying mechanisms for proinsulin transport are still not fully understood. We show that β cell-specific deletion of , also known as , leads to increased ER stress, reduced insulin biogenesis in the pancreas, and severe glucose intolerance in mice. We reveal that cTAGE5/MEA6 interacts with vesicle membrane soluble -ethyl-maleimide sensitive factor attachment protein receptor Sec22b. Sec22b and its interaction with cTAGE5/MEA6 are essential for proinsulin processing. cTAGE5/MEA6 may coordinate with Sec22b to control the release of COPII vesicles from the ER, and thereby the ER-to-Golgi trafficking of proinsulin. Importantly, transgenic expression of human cTAGE5/MEA6 in β cells can rescue not only the defect in islet structure, but also dysfunctional insulin biogenesis and glucose intolerance on / conditional knockout background. Together our data provide more insight into the underlying mechanism of the proinsulin trafficking pathway.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9525eISSN: 1540-8140DOI: 10.1083/jcb.201705027Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5716288
- Format
- –
- Schlagworte
- Animals, Antigens, Neoplasm - genetics, Antigens, Neoplasm - metabolism, Beta cells, Biosynthesis, Cells, Clonal deletion, COP-Coated Vesicles - metabolism, COP-Coated Vesicles - ultrastructure, Diabetes, Diabetes mellitus, Endoplasmic reticulum, Endoplasmic Reticulum - metabolism, Gene Deletion, Gene Expression Regulation, Genetic Complementation Test, Glucose, Glucose - metabolism, Glucose tolerance, Glucose Tolerance Test, Golgi apparatus, Golgi Apparatus - metabolism, Humans, Insulin, Insulin-Secreting Cells - cytology, Insulin-Secreting Cells - metabolism, Intolerance, Mice, Mice, Transgenic, Neoplasm Proteins - deficiency, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Pancreas, Proinsulin - biosynthesis, Protein Transport, R-SNARE Proteins - genetics, R-SNARE Proteins - metabolism, Rodents, Secretion