Fast, Ca2+-dependent exocytosis at nerve terminals: shortcomings of SNARE-based models.

•Presynaptic Ca2+ channels regulate fast, synchronous neurotransmitter release.•Synaptotagmins are the main Ca2+ sensors for regulated exocytosis at nerve terminals.•SNARE proteins are critical constituents of the exocytotic machinery at nerve endings.•How synaptotagmin regulates SNARE-driven membrane fusion remains controversial.•A new model of synaptotagmin-dependent membrane fusion is discussed.