Synaptotagmin: a Calcium Sensor on the Synaptic Vesicle Surface

TLDR

Neurons release neurotransmitters by calcium‑dependent exocytosis of synaptic vesicles, yet the molecular steps translating the calcium signal into membrane fusion remain unclear. Synaptotagmin, a conserved synaptic vesicle protein, binds calcium at physiological concentrations in complex with negatively charged phospholipids through its cytoplasmic domain, a process that requires its intact oligomeric structure and indicates it functions as a cooperative calcium receptor in exocytosis.

Abstract

Neurons release neurotransmitters by calcium-dependent exocytosis of synaptic vesicles. However, the molecular steps transducing the calcium signal into membrane fusion are still an enigma. It is reported here that synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids. This binding is specific for calcium and involves the cytoplasmic domain of synaptotagmin. Calcium binding is dependent on the intact oligomeric structure of synaptotagmin (it is abolished by proteclytic cleavage at a single site). These results suggest that synaptotagmin acts as a cooperative calcium receptor in exocytosis.