Exocytosis and Synaptic Vesicle Function

Abstract Synaptic vesicles release their vesicular contents to the extracellular space by Ca 2+ ‐triggered exocytosis. The Ca 2+ ‐triggered exocytotic process is regulated by synaptotagmin (Syt), a vesicular Ca 2+ ‐binding C2 domain protein. Synaptotagmin 1 (Syt1), the most studied major isoform among 16 Syt isoforms, mediates Ca 2+ ‐triggered synaptic vesicle exocytosis by interacting with the target membranes and SNARE/complexin complex. In synapses of the central nervous system, synaptobrevin 2, a major vesicular SNARE protein, forms a ternary SNARE complex with the plasma membrane SNARE proteins, syntaxin 1 and SNAP25. The affinities of Ca 2+ ‐dependent interactions between Syt1 and its targets (i.e., SNARE complexes and membranes) are well correlated with the efficacies of the corresponding exocytotic processes. Therefore, different SNARE protein isoforms and membrane lipids, which interact with Syt1 with various affinities, are capable of regulating the efficacy of Syt1‐mediated exocytosis. Otoferlin, another type of vesicular C2 domain protein that binds to the membrane in a Ca 2+ ‐dependent manner, is also involved in the Ca 2+ ‐triggered synaptic vesicle exocytosis in auditory hair cells. However, the functions of otoferlin in the exocytotic process are not well understood. In addition, at least five different types of synaptic vesicle proteins such as synaptic vesicle protein 2, cysteine string protein α, rab3, synapsin, and a group of proteins containing four transmembrane regions, which includes synaptophysin, synaptogyrin, and secretory carrier membrane protein, are involved in modulating the exocytotic process by regulating the formation and trafficking of synaptic vesicles. © 2014 American Physiological Society. Compr Physiol 4:149‐175, 2014.