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.

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

“…The assessment of synaptic proteins included synaptophysin, bassoon, synaptic Ras GTPase--activating protein 1 (SynGAP), and postsynaptic density protein 95 (PSD95). Synaptophysin and bassoon are two major presynaptic proteins that are localized in or associated with presynaptic vesicles (Elferink and Scheller, 1995;Schoch and Gundelfinger, 2006;Shin, 2014;Wiedenmann and Franke, 1985). On the other hand, SynGAP and PSD95 are two major postsynaptic proteins that are enriched at postsynaptic sites of excitatory synapses, where they critically help organizing and strengthening excitatory receptor complexes and their associated signaling proteins (Kim et al, 1998;Kim and Sheng, 2004;Sheng and Hoogenraad, 2007).…”

Regulation of Exocytosis by Complexin

“…Stimulations of neurons cause an increase in cytosolic Ca 2+ concentrations and trigger fusions of synaptic vesicles into the plasma membrane to release transmitters to the extracellular space [1][2][3] . Synaptotagmin 1 (Syt1), a vesicular Ca 2+ binding C2 domain protein, regulates Ca 2+ -triggered neurotransmitter release by interacting with membranes and the SNARE complex in a Ca 2+ -dependent manner [6,7] . Synaptobrevin 2 (Syb2; also known as vesicle-associated membrane protein 2, VAMP2), a vesicular SNARE protein, forms a ternary SNARE complex with Syntaxin and SNAP-25 that are located in the target plasma membrane [8] .…”

“…Synaptobrevin 2 (Syb2; also known as vesicle-associated membrane protein 2, VAMP2), a vesicular SNARE protein, forms a ternary SNARE complex with Syntaxin and SNAP-25 that are located in the target plasma membrane [8] . The interaction between Syt1 and the membrane is essential for the Ca 2+ -binding to the C2 domains of Syt1 in physiological Ca 2+ concentrations [7,9,10] . Meanwhile, the Ca 2+ -dependent affinities of interactions between Syt1 and SNARE complexes are correlated with the efficacies of the corresponding exocytosis [6] .…”

“…Synchronous release causes rapid actions, while asynchronous release triggers long-lasting actions of the target cells [7,21] . Both modes of release are required to maintain the functions of biological systems.…”

“…Both modes of release are required to maintain the functions of biological systems. In addition, neurons are also capable of releasing neurotransmitters without evoked stimulations but still mainly in a Ca 2+ -dependent manner, which is called spontaneous release ( Figure 2A) [7,21] . Four Cpx isoforms (Cpx1-4) are expressed mainly in the nervous system such as the brain, spinal cord, and retina, where neurotransmitters are released in a synchronous manner ( Figure 2A) [13,16] .…”