Synaptic vesicle protein 2 (SV2) and Synaptosomal-associated protein 25 (SNAP-25) (SV2/SNAP-25)

Synaptic vesicle protein 2 (SV2) and Synaptosomal-associated protein 25 (SNAP-25) constitute the dual-stage target system for Botulinum neurotoxin type A (BoNT/A) in cholinergic motor neurons. SV2 is a transmembrane protein located on synaptic vesicles that is exposed on the presynaptic membrane during exocytosis, serving as the high-affinity receptor for toxin binding and internalization (Science, 2006, 312(5773):592-596). SNAP-25 is a t-SNARE protein essential for the calcium-dependent fusion of acetylcholine-containing vesicles with the presynaptic plasma membrane (UniProt P60880). Upon entry into the neuron, the light chain of BoNT/A enzymatically cleaves SNAP-25, which prevents the assembly of the functional SNARE complex and blocks the release of acetylcholine into the neuromuscular junction (StatPearls: Botulinum Toxin). This mechanism results in localized muscle relaxation and is therapeutically exploited to treat conditions such as cervical dystonia, spasticity, chronic migraine, and various cosmetic concerns (FDA Label: Botox; Mayo Clinic).

Other names

SV2ASV2BSV2CSNAP25SNARE complexBotulinum toxin type A targetSynaptosomal-associated 25 kDa protein

Botulinum toxin type A binds to Synaptic Vesicle Protein 2 (SV2) on the presynaptic membrane of cholinergic neurons (Science, 2006). Following endocytosis, the toxin's light chain is released into the cytosol where it proteolytically cleaves SNAP-25 (PubMed: 16543415). This cleavage prevents the formation of the SNARE complex, thereby inhibiting the fusion of acetylcholine vesicles with the presynaptic membrane and blocking neuromuscular transmission (StatPearls).