Synaptic vesicle cycle (umbrella)

The life cycle of the synaptic vesicle at a presynaptic terminal, modeled as an organelle lifecycle with five stages: (1) neurotransmitter loading, in which the V-ATPase acidifies the lumen and a vesicular transporter fills the vesicle; (2) reserve-pool clustering, in which synapsins tether loaded vesicles into a phase-separated cluster from which they are mobilised on demand; (3) exocytosis, in which vesicles are recruited to the active zone, primed by Munc13/Munc18-1, and fused by the SNARE machinery when synaptotagmin senses Ca2+ entering through Cav2 channels; (4) endocytosis, in which vesicle membrane and proteins are retrieved by clathrin-dependent or ultrafast/bulk routes and re-formed by dynamin fission and auxilin/HSC70 uncoating; and (5) maturation, in which the regenerated vesicle regains its full protein complement and is returned to the loading stage. Stages 1, 3 and 4 are elaborated in separate modules; this umbrella carries the cycle topology and the hallmark machinery of each stage. Exemplars are human; the cycle is conserved at metazoan chemical synapses. Grounded in GO:0099504 (synaptic vesicle cycle).

Umbrella over MODULE:synaptic_vesicle_neurotransmitter_loading, MODULE:synaptic_vesicle_exocytosis and MODULE:synaptic_vesicle_endocytosis. Each stage node here carries only the hallmark participants needed to identify the stage; the detailed decomposition (variants, complexes, PAINT anchors) lives in the stage modules. Reserve-pool clustering and vesicle maturation are modeled directly here because they do not warrant standalone modules. Dense-core vesicle and neuropeptide release are out of scope. Caenorhabditis elegans orthologs are listed as second representative members throughout: the worm realizes every stage with single-copy genes (vha-13, eat-4, snn-1, unc-64/ric-4/snb-1, snt-1, chc-1, dyn-1), so the vertebrate variant sets collapse to one gene each. The one exception is the maturation part: the worm synaptophysin sph-1 is expressed mainly in pharyngeal and sphincter muscle rather than neurons, and scm-1 sph-1 sng-1 triple mutants have normal synapses (PMID:16698939), so no worm member is listed for the synaptophysin annoton; the pan-neuronal worm tetraspan vesicle protein is the synaptogyrin sng-1, which belongs to a different family.