Botulinum neurotoxin receptor complex (BoNT receptor complex)

The Botulinum neurotoxin receptor complex is a multi-component system located on the presynaptic membranes of cholinergic neurons, primarily at the neuromuscular junction. It consists of polysialogangliosides (such as GT1b and GD1a) which serve as initial low-affinity binding sites, and specific synaptic vesicle proteins that act as high-affinity receptors: Synaptic Vesicle Protein 2 (SV2) for serotypes A, E, and D, and Synaptotagmin (Syt I/II) for serotypes B, G, and DC [1, 2, 3]. This double-receptor mechanism ensures the extreme neurospecificity and potency of botulinum neurotoxins (BoNTs) [7, 11]. Upon binding, the toxin is internalized via synaptic vesicle recycling (endocytosis), allowing the light chain to enter the cytosol and cleave SNARE proteins, thereby blocking the release of the neurotransmitter acetylcholine [4, 12]. While these receptors are the gateway for botulism-inducing toxins, they are also the therapeutic targets for clinical BoNT preparations used to treat conditions like muscle spasticity, dystonia, and chronic migraine [10, 14]. Additionally, the SV2A component is the primary target for the antiepileptic drugs levetiracetam and brivaracetam [5, 10].

Other names

Synaptic vesicle protein 2 / synaptotagmin and polysialogangliosides on cholinergic presynaptic terminalsSV2/Syt/Ganglioside complexBotulinum toxin receptorDual-receptor complex for BoNTSynaptic vesicle protein 2SynaptotagminPolysialogangliosides

Botulinum neurotoxins bind to the receptor complex (gangliosides and protein receptors SV2 or synaptotagmin) on the presynaptic membrane, undergo endocytosis, and subsequently cleave SNARE proteins to inhibit the release of acetylcholine.