Choline acetyltransferase and vesicular acetylcholine transporter genes are the products of two adjacent genes defining a cholinergic locus. The release mechanism is expressed independently of this locus in some cell lines. A cholinergic neuron will therefore have to coordinate the expression of release with that of the cholinergic locus. Transfection of a plasmid encoding Torpedo mediatophore in cells that are unable to release this transmitter endows them with a Ca2(+)-dependent and quantal release mechanism. The synchronization of mediatophore activation results from a control of calcium microdomains by the synaptic vesicles. It is therefore dependent on the proteins that dock vesicles close to calcium channels.