Roles of calmodulin and calmodulin-binding proteins in synaptic vesicle recycling during regulated exocytosis at submicromolar Ca²⁺ concentrations

Calcium ion is required at various concentrations for vesicular recycling in the presynaptic terminal. Although calmodulin (CaM) is the most abundant Ca²⁺-binding protein and has a submicromolar affinity for Ca²⁺, it is not the Ca²⁺ sensor for vesicular fusion because this process requires Ca²⁺ concentrations above 1 μM. Several lines of evidence, however, suggest that CaM mediates the regulation of vesicular recycling by submicromolar Ca²⁺ via novel protein-protein interactions. In this review, we discuss recent findings on how CaM regulates synaptic vesicle recycling by controlling the SNARE mechanism, which is the molecular machinery that mediates exocytosis.