Protein-protein interactions and protein modules in the control of neurotransmitter release

Information transfer among neurons is operated by neurotransmitters stored in synaptic vesicles and released to the extracellular space by an efficien t process of regulated exocytosis. Synaptic vesicles are organized into two distinct functional pools, a large reserve pool in which vesicles are rest rained by the actin-based cytoskeleton, and a quantitatively smaller releas able pool in which vesicles approach the presynaptic membrane and eventuall y fuse with it on stimulation. Both synaptic vesicle trafficking and neurot ransmitter release depend on at precise sequence of events that include rel ease from the reserve pool, targeting to the active zone, docking, priming, fusion;Ind endocytotic retrieval of synaptic vesicles. These steps are med iated by a series of specific interactions among cytoskeletal, synaptic ves icle, presynaptic membrane and cytosolic proteins that, by acting in concer t, promote the spatial and temporal regulation of the exocytotic machinery. The majority of these interactions are mediated by specific protein module s and domains that are found in many proteins and are involved in numerous intracellular processes. In this paper, the possible physiological role of these multiple protein-protein interactions is analysed, with ensuing updat ing and clarification of the present molecular model of the process of neur otransmitter release.