Mediatophore and other presynaptic proteins. A cybernetic linking at the active zone

In rapidly transmitting synapses, the mediatophore, a protein located in the presynaptic membrane, seems to play a key role in the last step of transmitter release. Reconstituted either in proteoliposomes or in Xenopus oocytes, or transfected in particular cell lines, the mediatophore is able to release acetylcholine with characteristics which meet several typical features of transmitter release in natural synapses. Good correspondence between the two conditions was found for: i) the dependency of release upon calcium concentration; ii) the desensitisation of release by persistence of internal calcium; iii) the effect of several drugs; iv) the fleeting formation of a population of large intramembrane particles during the precise time of release; and v) the pulsatile or quantal nature of transmitter release. All these features therefore could well be ascribed to intrinsic properties of the mediatophore molecule. How is the mediatophore integrated in the whole presynaptic apparatus? To what extent is its function regulated by the other proteins of the active zone? These questions are far from being solved. We want nevertheless to propose here a general view in which characteristic presynaptic functions such as transmitter release, calcium entry, sequestration and extrusion, regulation of short- and long-term changes in release efficiency, are supported by an ordered succession of molecular events involving the proteins of the active zone. It will be seen that some proteins compete for a common binding site. It is thus expected that they will occupy this site in a regulated succession, according to simple cybernetic rules.