Synaptotagmin is not only a calcium sensor, but also exerts entropic forces that drive membrane fusion

Synaptic neurotransmitter (NT) release is accomplished by a cellular machinery that senses presynaptic Ca-entry following an action potential, and responds by fusing the vesicle and plasma membranes for NT release through the fusion pore. In a long-standing view, a clear division of labor exists between Synaptotagmin 1 (Syt1), the Ca sensor for synchronous release, and the SNAREs which catalyze membrane fusion. Here we developed molecular dynamics simulations suggesting that, surprisingly, Syt1 also plays a major role in membrane fusion. Our findings are strongly supported by experiments. A picture of the release machinery emerges in which both SNAREs and Syt1 exert entropic forces that drive fusion.