Depolarization-evoked synaptic transmission relies on the Ca2+-regulated release of quantal packets of neurotransmitters following the fusion of synaptic vesicles with the presynaptic plasma membrane. It is well known that neuronal voltage-gated Ca2+ channels (VGCC), mainly of the CaV2.1 and CaV2.2 subtypes, play a key role in the first steps of this process, by controlling extracellular Ca2+ influx into active zones of the synapse. These channels are in close association with the vesicle machinery and interact with several members of SNARE proteins (soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein receptor) including syntaxin 1A/1B and SNA P-25 (Q-SNARE s), and synaptotagmin 1 and synaptobrevin 2 (R-SNARE s) (reviewed in ref. ). All bind to the synprint (synaptic protein interaction) motif within the intracellular II -III linker of CaV2.1 and CaV2.2 channels and are responsible for a bidirectional coupling (i) linking the Ca2+ influx with the synaptic vesicle release machinery, which is essential for efficient, fast and spatially delimited neurotransmitter release and (ii) providing regulation of Ca2+ channel activity and thus of Ca2+ influx.展开▼