Synaptic vesicle glycoprotein 2 and Synaptotagmin (SV2/Syt)

Synaptic vesicle glycoprotein 2 (SV2) and Synaptotagmin (Syt) are essential membrane proteins located on the inner surface of synaptic vesicles that function as the primary protein receptors for Botulinum Neurotoxins (BoNTs). SV2 isoforms (A, B, and C) are specifically recognized by the heavy chains of BoNT/A, BoNT/D, BoNT/E, and BoNT/F, while Synaptotagmin I and II serve as the receptors for BoNT/B, BoNT/G, and BoNT/DC (Rummel, 2013). These receptors become accessible on the neuronal surface only during vesicle exocytosis, at which point the toxin's heavy chain binds to the luminal domains of these proteins in a ganglioside-dependent manner (Dong et al., 2006). This high-affinity binding triggers receptor-mediated endocytosis, internalizing the toxin into acidic endosomes where the light chain is subsequently translocated into the cytosol. Once in the cytosol, the light chain acts as a zinc-dependent endopeptidase to cleave specific SNARE proteins, thereby inhibiting the release of acetylcholine at the neuromuscular junction (Dong et al., 2003). This mechanism is therapeutically exploited using various botulinum toxin preparations to treat medical conditions characterized by muscle overactivity, such as cervical dystonia, blepharospasm, and chronic migraine.

Other names

SV2ASV2BSV2CSyt1Syt2Botulinum neurotoxin receptorSynaptotagmin-1Synaptotagmin-2Synaptic vesicle protein 2

The heavy chain of botulinum neurotoxin binds to the luminal domains of SV2 or Synaptotagmin exposed during exocytosis, facilitating receptor-mediated endocytosis and subsequent translocation of the light chain into the neuronal cytosol (Rummel, 2013).