High Sensitivity of Mouse Neuronal Cells to Tetanus Toxin Requires a GPI-Anchored Protein

Tetanus neurotoxin (TeNT) produced by Clostridium tetani specifically cleaves VAMP/synaptobrevin (VAMP) in central neurons, thereby causing inhibition of neurotransmitter release and ensuing spastic paralysis. Although polysialogangliosides act as components of the neurotoxin binding sites on neuron...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-11, Vol.289 (2), p.623-629
Main Authors: Munro, Patrick, Kojima, Hiroshi, Dupont, Jean-Luc, Bossu, Jean-Louis, Poulain, Bernard, Boquet, Patrice
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacology
Binding Sites
Cells, Cultured
Cerebellum - metabolism
Clostridium tetani
Cytosol - chemistry
Dose-Response Relationship, Drug
Electrophysiology
Endocytosis
Filipin - metabolism
glycosylphosphatidylinositol
GPI-anchored protein
lipid rafts
Membrane Microdomains - metabolism
Mice
Mice, Inbred C57BL
Models, Biological
neuron
Neurons - metabolism
Neurons - physiology
Nystatin - metabolism
Phosphatidylinositol Diacylglycerol-Lyase
Phosphoinositide Phospholipase C
Protein Binding
Protein Structure, Tertiary
Purkinje Cells - metabolism
Spinal Cord - embryology
synaptobrevin
tetanus toxin
Tetanus Toxin - pharmacology
Time Factors
Type C Phospholipases - metabolism
VAMP protein
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Summary:Tetanus neurotoxin (TeNT) produced by Clostridium tetani specifically cleaves VAMP/synaptobrevin (VAMP) in central neurons, thereby causing inhibition of neurotransmitter release and ensuing spastic paralysis. Although polysialogangliosides act as components of the neurotoxin binding sites on neurons, evidence has accumulated indicating that a protein moiety is implicated as a receptor of TeNT. We have observed that treatment of cultured mouse neuronal cells with the phosphatidylinositol-specific phospholipase C (PIPLC) inhibited TeNT-induced cleavage of VAMP. Also, we have shown that the blocking effects of TeNT on neuroexocytosis can be prevented by incubation of Purkinje cell preparation with PIPLC. In addition, treatment of cultured mouse neuronal cells with cholesterol sequestrating agents such as nystatin and filipin, which disrupt clustering of GPI-anchored proteins in lipid rafts, prevented intraneuronal VAMP cleavage by TeNT. Our results demonstrate that high sensitivity of neurons to TeNT requires rafts and one or more GPI-anchored protein(s) which act(s) as a pivotal receptor for the neurotoxin.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.6031