Controversies in synaptic vesicle exocytosis.

At the heart of synaptic transmission resides the synaptic vesicle cycle – a membrane trafficking pathway in which small membrane-bound vesicles mediate the release of neurotransmitter from presynaptic terminals. The cycle resembles general membrane trafficking and has three phases: vesicle filling, release and recycling. During filling, neurotransmitter is loaded into vesicles via vesicular neurotransmitter transporters. It is then released by exocytosis: vesicles dock with the plasma membrane and undergo a maturation step, termed priming; then, following influx of calcium through voltage-gated channels, a calcium sensor promotes fusion of the vesicle with the plasma membrane. Membrane fusion consumes vesicle membrane and vesicle proteins; thus, these components must be recycled to sustain neurotransmitter release.