Synaptotagmin: Mechanisms of an electrostatic switch

Synaptic transmission relies on the fast, synchronous fusion of neurotransmitter filled vesicles with the presynaptic membrane. Synaptotagmin is the Ca²⁺ sensor that couples the Ca²⁺ influx into nerve terminals following an action potential with this fast, synchronous vesicle fusion. Over two decades of synaptotagmin research has provided many clues as to how Ca²⁺ binding by synaptotagmin may lead to vesicle fusion. In vitro studies of molecular binding interactions are essential for elucidating potential mechanisms. However, an in vivo system to evaluate the postulated mechanisms is required to determine functional significance. The neuromuscular junction (NMJ) has long been an indispensable tool for synaptic research and studies at the NMJ will undoubtedly continue to provide key insights into synaptotagmin function.