Voltage-gated calcium channel nanodomains: molecular composition and function.

Voltage-gated calcium (CaV ) channels and their regulation by proteins at the synaptic cleft play a critical role in neurotransmission. These interactions fine-tune the synaptic response through the regulation of Ca2+ entry into the presynaptic terminal and trigger the fusion of vesicles filled with neurotransmitters and peptides. Regulation of CaV channel intrinsic properties and their numbers at the active zones shape the timing and strength of synaptic function. Here, we provide an overview of a number of proteins reported to be part of CaV channel nanodomains at the synaptic cleft and the repercussions of these interactions for CaV channel trafficking, tethering at the active zone, and regulation of their biophysical properties. We summarize the current state of knowledge by which CaV channels are regulated at presynaptic sites.