Synaptic vesicle endocytosis and vesicle regeneration

The retrieval stage of the synaptic vesicle cycle, in which vesicle membrane and resident proteins deposited in the presynaptic plasma membrane by exocytosis are recovered and re-formed into release-competent vesicles at the presynaptic endocytic zone. In the classical clathrin-mediated route, the AP-2 adaptor complex, the neuron-specific assembly protein AP180 and the synaptotagmin-sorting adaptor stonin-2 recognise vesicle cargo and PI(4,5)P2 and nucleate a clathrin coat; BAR-domain proteins (endophilin, amphiphysin, syndapin) shape the invaginating membrane and recruit the GTPase dynamin, which constricts and severs the neck; synaptojanin-1 hydrolyses PI(4,5)P2 and auxilin recruits HSC70 to strip the clathrin coat, yielding a naked vesicle ready for re-acidification and loading. The same coat, curvature, fission and uncoating machinery is reused when membrane is first retrieved by clathrin-independent ultrafast or bulk endocytosis and vesicles are then regenerated by clathrin-dependent budding from a synaptic endosome. The module conforms, with stated deviations, to the generic MODULE:vesicle_coat_budding motif. Exemplars are human. Grounded in GO:0048488 (synaptic vesicle endocytosis).

Human-centric exemplars with family-level descriptors so the module stays reusable. The mechanistic parts (coat assembly, curvature, fission, uncoating) are shared by both retrieval routes; the root variant set records only where the coat forms (plasma membrane vs synaptic endosome). Kiss-and-run retrieval is not modeled. Stonin-2 and AP2M1 both belong to the AP-mu PANTHER family (PTHR10529); the two descriptors are kept as distinct roles, each grounded at family level so that the worm orthologs (unc-41, dpy-23) fit. Loading and release stages are in MODULE:synaptic_vesicle_neurotransmitter_loading and MODULE:synaptic_vesicle_exocytosis; MODULE:synaptic_vesicle_cycle is the umbrella. Caenorhabditis elegans orthologs are listed as second representative members (dpy-23, apb-1, apa-2, aps-2, unc-11, unc-41, chc-1, clic-1, unc-57, amph-1, sdpn-1, dyn-1, unc-26, dnj-25, hsp-1); the worm has one dynamin (dyn-1) and one endophilin (unc-57), and ultrafast endocytosis was first described at its neuromuscular junction. Two caveats from the worm gene reviews: amph-1 and sdpn-1 are grounded here by orthology only, since their worm literature covers intestinal endocytic recycling and nuclear positioning rather than synaptic vesicle retrieval; and the worm has a single beta-adaptin (apb-1) shared between AP-1 and AP-2, so its AP-1 annotations are correct rather than over-propagated.