Synaptic vesicle protein 2C (SV2C)

Synaptic vesicle protein 2C (SV2C) is a transmembrane glycoprotein localized to the membranes of synaptic vesicles, primarily within phylogenetically older regions of the brain such as the striatum, substantia nigra, and olfactory bulb (UniProt: Q496J9). As a member of the Major Facilitator Superfamily (MFS), it plays a specialized role in regulating calcium-dependent exocytosis and maintaining the readily releasable pool of neurotransmitters, particularly within dopaminergic neurons (PubMed: 25103173). SV2C is uniquely characterized as the high-affinity protein receptor for Botulinum neurotoxin type A (BoNT/A), serving as the gateway for the toxin's entry into nerve terminals (PubMed: 16543415). Clinically, SV2C has been implicated in the pathophysiology of Parkinson's disease and may influence the brain's response to nicotine in the basal ganglia (PubMed: 31110114). Due to its restricted expression pattern compared to its ubiquitous paralog SV2A, it represents a distinct therapeutic target for movement disorders and localized neurotoxin delivery.

Other names

Synaptic vesicle glycoprotein 2CSV2C

SV2C functions as a high-affinity protein receptor for Botulinum neurotoxin type A (BoNT/A); the toxin's heavy chain binds to the luminal domain of SV2C during vesicle recycling, which triggers endocytosis and internalization of the toxin into the presynaptic terminal (PubMed: 16543415). Endogenously, SV2C is thought to modulate neurotransmitter release by interacting with synaptotagmin-1 and regulating the calcium sensitivity of the vesicle fusion machinery (PubMed: 25103173).