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. 2000 Mar;49(3):383-91.
doi: 10.2337/diabetes.49.3.383.

Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis

H Brown  1 , B Meister, J Deeney, B E Corkey, S N Yang, O Larsson, C J Rhodes, S Seino, P O Berggren, G Fried
Affiliations

Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis

H Brown et al. Diabetes. 2000 Mar.

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.

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