Interaction between Clostridium botulinum neurotoxin and gangliosides

Kitamura, Masaru; Iwamori, Masao; Nagai, Yoshitaka

doi:10.1016/0304-4165(80)90382-7

Cited by 152 publications

(69 citation statements)

References 30 publications

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“…However, ganglia-~-tetraosyl ceramide with a monosialosyl residue at the internal galactose required a monosialosyl residue at the terminal (GDla) for binding and the presence of a disialosyl residue at the terminal (GTla) resulted rather in the loss of toxin binding. These results were somewhat different from those obtained from the detoxification experiment [8], which showed GTlb and GQlb to be the most potent inhibitors and GDla, GDlb and GTla to be moderate inhibitors. In view of both results obtained with the different procedures, it is certain that GQlb, GTlb and GDla are definitely involved in the C. botulinurn (type A) neurotoxin receptor.…”

Section: Discussioncontrasting

confidence: 99%

“…As shown in fig.2, GQlb was shown to be the most reactive with the toxin, and GTlb and GDla were also potential receptors for the toxin. However, unexpectedly, GDlb and GTla, both of which showed distinct neutralizing activity for the in vivo toxicity [8], were not able to be bound with the toxin. The toxin did not bind to GM3, GM2, GM1 and GD3.…”

Section: Interaction Of C Botulinurn Neurotoxin (Typementioning

confidence: 93%

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TLC immunostaining characterization of Clostridium botulinum type A neurotoxin binding to gangliosides and free fatty acids

et al. 1986

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Section: Discussioncontrasting

confidence: 99%

Section: Interaction Of C Botulinurn Neurotoxin (Typementioning

confidence: 93%

TLC immunostaining characterization of Clostridium botulinum type A neurotoxin binding to gangliosides and free fatty acids

et al. 1986

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“…Specifically, polysialylated gangliosides like GT1b (6) were shown to be involved in BoNT/A neurotoxicity (7,8). Since then, GT1b has been shown to inhibit BoNT/A binding to synaptosomes (9), to quench BoNT/A fluorescence (10), and to be bound by BoNT/A when it was immobilized on either a thin layer chromatogram (11) or on plastic wells (12). The dissociation constant for the adherence of BoNT/A-H C to GT1b-containing liposomes was recently reported to be ϳ10 Ϫ8 M (13).…”

mentioning

confidence: 99%

Botulinum Neurotoxin A Activity Is Dependent upon the Presence of Specific Gangliosides in Neuroblastoma Cells Expressing Synaptotagmin I

Yowler

Kensinger

Schengrund

2002

Journal of Biological Chemistry

127

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Botulinum neurotoxin A (BoNT/A) is the deadliest of all known biological substances. Although its toxicity makes BoNT/A a biological warfare threat, its biologic activity makes it an increasingly useful therapeutic agent for the treatment of muscular disorders. However, almost 200 years after its discovery, the neuronal cell components required for the activity of this deadly toxin have not been unequivocally identified. In this work, neuroblastoma cells expressing synaptotagmin I, a protein shown to be bound by BoNT/A, were used to determine whether specific gangliosides were necessary for BoNT/A activity as measured by synaptosomal-associated protein of 25 kDa (SNAP-25) cleavage. Ganglioside GT1b was found to support BoNT/A activity significantly more effectively than GD1a, which was far more effective than GM1 when added to ganglioside-deficient murine cholinergic Neuro 2a or to human adrenergic SK-N-SH neuroblastoma cells. Whereas both cell lines expressed synaptotagmin I, SNAP-25 cleavage was not observed in the absence of complex gangliosides. These results indicate that 1) gangliosides are required for BoNT/A activity, 2) synaptotagmin I in the absence of gangliosides does not support BoNT/A activity, and 3) Neuro 2a cells are an efficient model system for studying the biological activity of BoNT/A.

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“…Gangliosides are present in the plasma membrane of vertebrate cells with their oligosaccharide chains exposed to the external environment, and they have been implicated as cell surface receptors for several bacterial toxins. Purified tetanus neurotoxin (TeNT) (21) and botulinum neurotoxin (BoNT) (22) mainly interact with the b-series gangliosides GD3, GD1b, GT1b, and GQ1b. Cholera toxin binds with high affinity and specificity to the ganglioside GM1 (23).…”

mentioning

confidence: 99%