Synaptic vesicle protein 2 (SV2) (SV2)

The presynaptic neuronal receptors for the onabotulinumtoxinA heavy chain are a dual-receptor complex comprising Synaptic Vesicle Protein 2 (SV2) isoforms and polysialogangliosides (Dong et al., 2006; Rummel, 2013). The heavy chain of the toxin first interacts with gangliosides like GT1b on the neuronal membrane, which facilitates the initial enrichment of the toxin at the presynaptic terminal (Montecucco, 1986). Subsequently, the toxin binds with high affinity to the luminal domain of SV2 (specifically SV2A, SV2B, or SV2C) as the vesicle membrane is exposed during exocytosis (Mahrhold et al., 2006). This binding triggers receptor-mediated endocytosis, internalizing the toxin into the neuron. Once internalized, the toxin's light chain is released into the cytosol where it cleaves the SNAP-25 protein, effectively blocking the release of acetylcholine (Binz et al., 1994). This targeted disruption of neuromuscular transmission is the basis for the clinical use of onabotulinumtoxinA in treating conditions such as cervical dystonia, chronic migraine, and various forms of spasticity (FDA, 2010). Safety concerns primarily involve the potential for the toxin to spread beyond the injection site, leading to unintended muscle weakness or respiratory distress (Botox Prescribing Information).

Other names

SV2ASV2BSV2CBotulinum neurotoxin type A receptorBoNT/A receptorPolysialoganglioside receptorGT1b gangliosideGD1a ganglioside

The heavy chain of onabotulinumtoxinA binds to the SV2 receptor and gangliosides on the presynaptic nerve terminal, mediating the internalization of the toxin via endocytosis, which allows the light chain to enter the cytosol and cleave SNAP-25.