The docking of synaptic vesicles on the presynaptic membrane and their priming for fusion with it to mediate synaptic transmission of nerve impulses typically occur at structurally specialized regions on the membrane called active zones. Stable components of active zones include aggregates of macromolecules, 'active zone material' (AZM), attached to the presynaptic membrane, and aggregates of Ca(2+)-channels in the membrane, through which Ca(2+) enters the cytosol to trigger impulse-evoked vesicle fusion with the presynaptic membrane by interacting with Ca(2+)-sensors on the vesicles. This laboratory has used electron tomography to study, at macromolecular spatial resolution, the structure and function of AZM at the simply arranged active zones of axon terminals at frog neuromuscular junctions. The results support the conclusion that AZM directs the docking and priming of synaptic vesicles and essential positioning of Ca(2+)-channels relative to the vesicles' Ca(2+)-sensors. Here we review the findings and comment on their applicability to understanding mechanisms of docking, priming and Ca(2+)-triggering at other synapses, where the arrangement of active zone components differs.
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