Synaptic vesicle glycoprotein 2C (SV2C) (SV2C)

Synaptic vesicle glycoprotein 2C (SV2C) is a member of the SV2 family of integral membrane proteins found in the membranes of synaptic vesicles (UniProt). It serves as the high-affinity neuronal protein receptor for Botulinum neurotoxin type A (BoNT/A), a potent neurotoxin that causes botulism by blocking acetylcholine release at the neuromuscular junction (PubMed). The toxin binds to the fourth luminal domain of SV2C, often in conjunction with ganglioside co-receptors, to trigger its internalization via endocytosis (NIH). Once inside the neuron, the toxin's light chain cleaves the SNARE protein SNAP-25, leading to flaccid paralysis (StatPearls). Beyond its role as a toxin receptor, SV2C is highly expressed in dopaminergic neurons of the basal ganglia and is involved in regulating dopamine release and homeostasis (PubMed). Genetic variations in SV2C have been associated with Parkinson's disease risk and the efficacy of dopaminergic therapies (NIH). While BoNT/A is used clinically for treating conditions such as cervical dystonia and chronic migraine, other drugs like levetiracetam target the SV2 family to modulate synaptic transmission in epilepsy (PubMed).

Other names

SV2CSynaptic vesicle protein 2CSLC22B3Solute carrier family 22 member B3KIAA1054

Botulinum neurotoxin type A binds to the luminal domain of SV2C to facilitate its internalization into neurons, where it subsequently cleaves SNAP-25 to inhibit acetylcholine release. Other drugs in the SV2 ligand class, such as levetiracetam, bind to SV2 proteins to modulate synaptic vesicle exocytosis and reduce neuronal excitability.