The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves

Mahrhold, Stefan; Rummel, Andreas; Bigalke, Hans; Davletov, Bazbek; Binz, Thomas

doi:10.1016/j.febslet.2006.02.074

Cited by 296 publications

(257 citation statements)

References 21 publications

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“…Subsequently, the toxin heavy chain binds its high affinity membrane protein acceptors, synaptic vesicle protein 2 (SV2) and fibroblast growth factor receptor 3, which govern BoNT/A binding and endocytotic entry into neurons (Dong et al, 2006;Jacky et al, 2013;Mahrhold et al, 2006). BoNT/A internalization into neurons may be mediated by all isoforms of SV2 (SV2 A-C), with the strongest affinity for SV2C (Dong et al, 2006).…”

Section: 3 Bont/a Internalization Into Nerve Terminalsmentioning

confidence: 99%

Botulinum toxin A, brain and pain

Matak

Lacković

2014

Progress in Neurobiology

149

114

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Section: 3 Bont/a Internalization Into Nerve Terminalsmentioning

confidence: 99%

Botulinum toxin A, brain and pain

Matak

Lacković

2014

Progress in Neurobiology

149

114

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“…[13][14][15][16] Studies on cultured hippocampal neurons from the rat or mouse phrenic nerve of the hemidiaphragm have shown that BTX-A recognizes and enters the ganglioside during neurotransmitter exocytosis when more-active receptors are exposed, exploiting the secretory vesicle recycling pathway. 17,18 Thus, endocytosis of BTX-A is enhanced by synaptic activity. 17,19 Once internalization has occurred, the BTX-A activity remains within the vicinity of the nerve terminal.…”

Section: Binding and Internalizationmentioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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“…Each NT recognizes a distinct receptor. Synaptotagmin II associated with ganglioside G T1b has been assigned as protein receptor of BoNT/B and BoNT/G, and synaptic vesicle membrane protein SV2 as receptor of BoNT/A (Nishiki et al, 1994(Nishiki et al, , 1996Rummel et al, 2004a;Dong et al, 2006;Mahrhold et al, 2006). Specific cell surface receptors account for the different sensitivity of cells and animal species to BoNTs and TeNT and play a major role in the subsequent intracellular trafficking.…”

Section: Transcytotic Pathway and Gangliosides: The Case Of Clostridimentioning

confidence: 99%

Bacterial protein toxins and lipids: role in toxin targeting and activity

Geny

Popoff

2006

Biology of the Cell

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All bacterial toxins, which globally are hydrophilic proteins, interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. Intracellular active toxins follow various trafficking pathways, the sorting of which is greatly dependent on the nature of the receptor, notably lipidic receptor or receptor embedded into a distinct environment such as lipid microdomains. Numerous other toxins act locally on cell membrane. Indeed, phospholipase activity is a common mechanism shared by several membrane‐damaging toxins. In addition, many toxins active intracellularly or on cell membrane modulate host cell phospholipid pathways. Unusually, a few bacterial toxins require a lipid post‐translational modification to be active. Thereby, lipids are obligate partners of bacterial toxins.

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The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves

Cited by 296 publications

References 21 publications

Botulinum toxin A, brain and pain

Botulinum toxin A, brain and pain

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Bacterial protein toxins and lipids: role in toxin targeting and activity

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