Calcium-dependent docking of synaptic vesicles.

The concentration of calcium ions in presynaptic terminals regulates transmitter release, but underlying mechanisms have remained unclear. Here we review recent studies that shed new light on this issue. Fast-freezing electron microscopy and total internal reflection fluorescence microscopy studies reveal complex calcium-dependent vesicle movements including docking on a millisecond time scale. Recordings from so-called 'simple synapses' indicate that calcium not only triggers exocytosis, but also modifies synaptic strength by controlling a final, rapid vesicle maturation step before release. Molecular studies identify several calcium-sensitive domains on Munc13 and on synaptotagmin-1 that are likely involved in bringing the vesicular and plasma membranes closer together in response to calcium elevation. Together, these results suggest that calcium-dependent vesicle docking occurs in a wide range of time domains and plays a crucial role in several phenomena including synaptic facilitation, post-tetanic potentiation, and neuromodulator-induced potentiation.