Publications from the Jorgensen Laboratory

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. The synaptic vesicle cycle is driven by members of protein families required for general membrane trafficking, including SNAREs, UNC-18, Rab3 and vacuolar H+ ATPases (V-ATPases), and unique proteins, such as synaptotagmin, which regulate aspects of exocytosis unique to synapses. Although extensively studied, the precise roles of these proteins remain controversial. Here we survey current models proposed for their function in synaptic vesicle cycling.