Synaptic vesicle endocytosis: calcium works overtime in the nerve terminal.

The functions of Ca2+ are many and varied within cells, but in the nerve terminals of neurons it has had a very defined role. That is, the influx of extracellular Ca2+ through voltage-dependent Ca2+ channels stimulates neurotransmitter release by exocytosis. For years this was assumed to be the main role for Ca2+ in this specialized subcellular region. However recent studies have shown that Ca2+ also has multiple roles in synaptic-vesicle endocytosis. This review will present evidence for three Ca2+-dependent and -independent steps; a high-affinity Ca2+-dependent triggering step, a Ca2+-independent maintenance phase, and a low-affinity Ca2+-dependent inhibition step. How the control of endocytosis by Ca2+ might impact on different neuronal functions such as synaptic transmission, the nucleation of SV endocytosis, and the repair of damaged membrane is then discussed.