Synaptic vesicle protein 2 and Synaptotagmin (SV2/Syt)

Synaptic vesicle protein 2 (SV2) and Synaptotagmin (Syt) are integral membrane proteins located on the luminal surface of synaptic vesicles within presynaptic nerve terminals. They serve as the high-affinity protein receptors for Botulinum neurotoxins (BoNTs), which are potent inhibitors of neurotransmitter release (Dong et al., 2006). SV2 isoforms (A, B, and C) are the primary receptors for BoNT/A, BoNT/D, BoNT/E, and BoNT/F, while Synaptotagmin I and II serve as receptors for BoNT/B and BoNT/G (Dong et al., 2003). Upon binding to these receptors during the process of vesicle recycling, the toxins are internalized via endocytosis into cholinergic neurons. Once inside, the light chain of the toxin is translocated into the cytosol, where it cleaves specific SNARE proteins (such as SNAP-25 or VAMP), effectively blocking the release of acetylcholine at the neuromuscular junction (Pirazzini et al., 2017). This mechanism is exploited therapeutically to treat conditions characterized by muscle overactivity, such as dystonia and spasticity, as well as chronic migraine and hyperhidrosis (StatPearls, 2023).

Other names

SV2SynaptotagminBotulinum neurotoxin receptorsBoNT receptorsSV2ASV2BSV2CSyt ISyt IISynaptic vesicle protein 2ASynaptotagmin-1Synaptotagmin-2

Botulinum neurotoxins bind to the luminal domains of SV2 or Synaptotagmin during vesicle recycling, facilitating their internalization into the presynaptic terminal where they subsequently cleave SNARE proteins to inhibit acetylcholine release.