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J Biol Chem, Vol. 274, Issue 35, 25173-25180, August 27, 1999
Neuronal Sensitivity to Tetanus Toxin Requires Gangliosides
Lura C.
Williamson ,
Karen E.
Bateman ,
Julianne C. M.
Clifford§, and
Elaine A.
Neale
From the Laboratory of Developmental Neurobiology,
NICHHD, National Institutes of Health, Bethesda, Maryland
20892-4480 and the § Center for Biologics Evaluation and
Research, Food and Drug Administration, Bethesda,
Maryland 20892
Tetanus toxin produces spastic paralysis in
situ by blocking inhibitory neurotransmitter release in the
spinal cord. Although di- and trisialogangliosides bind tetanus toxin,
their role as productive toxin receptors remains unclear. We examined
toxin binding and action in spinal cord cell cultures grown in the
presence of fumonisin B1, an inhibitor of ganglioside
synthesis. Mouse spinal cord neurons grown for 3 weeks in culture in 20 µM fumonisin B1 develop dendrites, axons, and
synaptic terminals similar to untreated neurons, even though thin layer
chromatography shows a greater than 90% inhibition of ganglioside
synthesis. Absence of tetanus and cholera toxin binding by
toxin-horseradish peroxidase conjugates or immunofluorescence further
indicates loss of mono- and polysialogangliosides. In contrast to
control cultures, tetanus toxin added to fumonisin
B1-treated cultures does not block potassium-stimulated glycine release, inhibit activity-dependent uptake of
FM1-43, or abolish immunoreactivity for vesicle-associated membrane
protein, the toxin substrate. Supplementing fumonisin
B1-treated cultures with mixed brain gangliosides
completely restores the ability of tetanus toxin to bind to the
neuronal surface and to block neurotransmitter release. These data
demonstrate that fumonisin B1 protects against
toxin-induced synaptic blockade and that gangliosides are a necessary
component of the receptor mechanism for tetanus toxin.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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