Neurotransmitter loading into synaptic vesicles

The vesicle-filling stage of the synaptic vesicle cycle. The vacuolar-type H+-ATPase on the synaptic vesicle membrane hydrolyses ATP to pump protons into the lumen, generating a proton electrochemical gradient (a pH gradient plus a lumen-positive membrane potential). A vesicular neurotransmitter transporter then uses that gradient to concentrate transmitter into the vesicle against a steep concentration gradient. The transporter identity sets the transmitter phenotype of the terminal: VGLUT1/2/3 (SLC17A6/7/8) for glutamate, VGAT (SLC32A1) for GABA and glycine, VMAT2 (SLC18A2) for monoamines, and VAChT (SLC18A3) for acetylcholine. The module is modeled with human exemplars but the acidify -> load topology is conserved across metazoan chemical synapses. Grounded in GO:0098700 (neurotransmitter loading into synaptic vesicle) and GO:0097401 (synaptic vesicle lumen acidification).

Human-centric exemplars; family-level descriptors are used so the module remains reusable. The V-ATPase is represented by three role-bearing subunits (catalytic A, proteolipid c ring, membrane a1 subunit) rather than the full fourteen-subunit complex. The transporter variant set is ONE_OR_MORE because some terminals co-release two transmitters. Detailed exocytosis and endocytosis stages are in MODULE:synaptic_vesicle_exocytosis and MODULE:synaptic_vesicle_endocytosis; the umbrella cycle is MODULE:synaptic_vesicle_cycle. Caenorhabditis elegans orthologs are listed as second representative members (vha-13, vha-1, unc-32, eat-4, unc-47, cat-1, unc-17); the worm has one gene per transporter role, so the neurotransmitter variant set maps one-to-one.