Synaptic vesicle glycoprotein 2 (SV2)

Synaptic vesicle glycoprotein 2 (SV2) is a family of integral membrane proteins found on all secretory and synaptic vesicles within neurons and endocrine cells. There are three isoforms—SV2A, SV2B, and SV2C—with similar structure but distinct expression patterns. Each isoform contains twelve transmembrane domains with cytoplasmic N-and C-terminal regions. The primary function attributed to these proteins is the regulation of action potential-dependent neurotransmitter release through modulation of calcium sensitivity during exocytosis. They are not directly involved in transporting neurotransmitters but play critical roles in maintaining the pool and readiness state (“priming”) of releasable synaptic vesicles. SV2 proteins also serve as entry points for certain neurotoxins such as botulinum toxin into neurons. Of particular clinical importance is the isoform SV2A, which serves as the molecular target for several antiepileptic drugs including levetiracetam and brivaracetam—these agents bind at a conserved site within the protein's transmembrane region. Loss or dysfunction of these proteins can result in profound neurological deficits including epilepsy; they have also been implicated more broadly in neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.

Other names

Synaptic vesicle protein 2SV2ASV2BSV2CSynaptic vesicle glycoprotein 2A/B/C

Antiepileptic drugs bind to a conserved central site on SV2A, stabilizing it in an inhibited transporter conformation that may modulate neurotransmitter release by affecting synaptic vesicle exocytosis