Mechanisms of Synaptic Vesicle Exo- and Endocytosis

Within 1 millisecond of action potential arrival at presynaptic terminals voltage–gated Ca²⁺ channels open. The Ca²⁺ channels are linked to synaptic vesicles which are tethered by active zone proteins. Ca²⁺ entrance into the active zone triggers: (1) the fusion of the vesicle and exocytosis, (2) the replenishment of the active zone with vesicles for incoming exocytosis, and (3) various types of endocytosis for vesicle reuse, dependent on the pattern of firing. These time-dependent vesicle dynamics are controlled by presynaptic Ca²⁺ sensor proteins, regulating active zone scaffold proteins, fusion machinery proteins, motor proteins, endocytic proteins, several enzymes, and even Ca²⁺ channels, following the decay of Ca²⁺ concentration after the action potential. Here, I summarize the Ca²⁺-dependent protein controls of synchronous and asynchronous vesicle release, rapid replenishment of the active zone, endocytosis, and short-term plasticity within 100 msec after the action potential. Furthermore, I discuss the contribution of active zone proteins to presynaptic plasticity and to homeostatic readjustment during and after intense activity, in addition to activity-dependent endocytosis.