Tetanus toxin potently stimulates tissue transglutaminase. A possible mechanism of neurotoxicity.
The observation that tetanus toxin (TT) contains two sequences that show homology to known transglutaminase (TGase) substrate sites suggested that the toxin and TGase might interact. This prediction was confirmed by two pieces of evidence. First, TT potently stimulated the enzymatic activity of TGase. The effect was maximal at physiological (micromolar) concentrations of the endogenous TGase regulators calcium and GTP. Second, TT and TGase displayed marked variations of their intrinsic fluorescence properties when they were coincubated, indicating the occurrence of binding between them. TT-TGase binding and TGase activation occurred at similar concentrations of TT and are probably causally related. The activation of TGase, an enzyme present in nerve endings that, when activated, can irreversibly cross-link cellular proteins, might mediate the neurotoxic action of TT.
Laboratory of Molecular Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro, Chieti, Italy.
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D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D005260:Female; D005454:Fluorescence Polarization; D006168:Guinea Pigs; D051379:Mice; D008969:Molecular Sequence Data; D009420:Nervous System / Q000187:drug effects*; D012689:Sequence Homology, Nucleic Acid; D013095:Spermidine / Q000378:metabolism; D013379:Substrate Specificity; D013744:Tetanus Toxin / Q000633:toxicity*; D011503:Transglutaminases / Q000378:metabolism*
D013744:Tetanus Toxin; D011503:Transglutaminases; D013095:Spermidine