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- Title
Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis.
- Authors
Brown, Hilary; Meister, Bjorn; Deeney, Jude; Corkey, Barbara E.; Yang, Shao-Nian; Larsson, Olof; Rhodes, C.J.; Seino, Susumu; Berggren, Per-Olof; Fried, Gabriel; Brown, H; Meister, B; Deeney, J; Corkey, B E; Yang, S N; Larsson, O; Seino, S; Berggren, P O; Fried, G
- Abstract
Synaptotagmin is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+-dependent secretory process. Previous studies of pancreatic beta-cells were unable to show presence of synaptotagmin I. We now present biochemical and immunohistochemical data showing that synaptotagmin III is present in pancreatic beta-cells as well as in the insulin-secreting cell line HIT-T15 and in rat insulinoma. By subcellular fractionation, we found synaptotagmin III in high-density fractions together with insulin and secretogranin I, indicating colocalization of synaptotagmin III and insulin in secretory granules. We could also show that blockade of synaptotagmin III by a specific antibody inhibited Ca2+-induced changes in beta-cell membrane capacitance, suggesting that synaptotagmin III is part of the functional protein complex regulating beta-cell exocytosis. The synaptotagmin III antibody did not affect the activity of the voltage-gated L-type Ca2+-channel. These findings are compatible with the view that synaptotagmin III, because of its distinct localization in the pancreatic beta-cell, functionally modulates insulin exocytosis. This indicates that synaptotagmin may have a general role in the regulation of exocytosis not only in neuronal cells but also in endocrine cells.
- Subjects
MEMBRANE proteins; EXOCYTOSIS; CELL compartmentation; PHYSIOLOGY
- Publication
Diabetes, 2000, Vol 49, Issue 3, p383
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.49.3.383