Synaptotagmins bind calcium to release insulin.

Plasma insulin levels are determined mainly 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 multiprotein SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes. However, fusion of the two membranes will proceed only in the presence of Ca(2+) ions, implicating a Ca(2+) sensor protein. The synaptotagmin gene family, comprising 15 members, was proposed to act as such Ca(2+) sensor in regulated exocytosis in neurons and 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.