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Am J Physiol Endocrinol Metab (August 19, 2008). doi:10.1152/ajpendo.90568.2008
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Submitted on July 7, 2008
Revised on August 15, 2008
Accepted on August 18, 2008

Synaptotagmins bind calcium to release insulin

Benoit R Gauthier1 and Claes B Wollheim1*

1 University of Geneva

* To whom correspondence should be addressed. E-mail: Claes.Wollheim{at}medecine.unige.ch.

Plasma insulin levels are mainly determined by the rate of exocytosis of the insulin-containing large dense core vesicles (LDCVs) of pancreatic islet {beta}-cells. This process involves the recruitment of LDCVs to the plasma membrane where they are docked by the assembly of multi-protein SNARE complexes. However, fusion of the two membranes will proceed only in the presence of Ca2+ ions implicating a Ca2+ sensor protein. The synaptotagmin gene family comprising 15 members was proposed to act as such Ca2+ sensor in regulated exocytosis in neurons, neuroendocrine and endocrine cells. Herein, we review the physiological function of the various synaptotagmins with reference to their impact on insulin exocytosis. Cumulating evidence emphasizes the crucial role of synaptotagmin VII and IX as mediators of glucose-induced insulin secretion.




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