Synaptotagmin: A Ca2+ sensor that triggers exocytosis?

Abstract

It has been fifty years since the discovery that Ca²⁺ triggers the rapid exocytosis of neurotransmitters from neurons. One of the proteins that has a crucial role in this secretion event is synaptotagmin I, an abundant constituent of synaptic vesicles that binds Ca²⁺ ions through two C2 domains. These properties prompted the idea that synaptotagmin I might function as a Ca²⁺ -sensor that triggers neurotransmitter release. So does synaptotagmin trigger exocytosis in a Ca²⁺ -dependent manner, and, if so, how does it operate?