Ca2+-dependent regulation of synaptic vesicle endocytosis

Abstract

Action potentials, when arriving at presynaptic terminals, elicit Ca(2+) influx through voltage-gated Ca(2+) channels. Intracellular [Ca(2+)] elevation around the channels subsequently triggers synaptic vesicle exocytosis and also induces various protein reactions that regulate vesicle endocytosis and recycling to provide for long-term sustainability of synaptic transmission. Recent studies using membrane capacitance measurements, as well as high-resolution optical imaging, have revealed that the dominant type of synaptic vesicle endocytosis at central nervous system synapses is mediated by clathrin and dynamin. Furthermore, Ca(2+)-dependent mechanisms regulating endocytosis may operate in different ways depending on the distance from Ca(2+) channels: (1) intracellular Ca(2+) in the immediate vicinity of a Ca(2+) channel plays an essential role in triggering endocytosis, and (2) intracellular Ca(2+) traveling far from the channels has a modulatory effect on endocytosis at the periactive zone. Here, I integrate the latest progress in this field to propose a compartmental model for regulation of vesicle endocytosis at synapses and discuss the possible roles of presynaptic Ca(2+)-binding proteins including calmodulin, calcineurin and synaptotagmin.