The role of transglutaminase in the mechanism of action of tetanus toxin

Julie A. Coffield, Robert Considine, Janet Jeyapaul, Andrew B. Maksymowych, Ren De Zhang, Lance L. Simpson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Tetanus toxin is a zinc-dependent metalloendoprotease that cleaves synaptobrevin, a polypeptide found in the membranes of synaptic vesicles. This action is thought to account for toxin-induced blockade of transmitter release. However, Facchiano and Luini (Facchiano, F., and Luini, A. (1992) J. Biol Chem. 267, 13267-13271) have proposed that tetanus toxin can stimulate transglutaminase, and Facchiano et al. (Facchiano, F., Benfenati, F., Valtorta, F., and Luini, A. (1993) J. Biol Chem. 268, 4588-4591) have further proposed that the stimulated enzyme produces cross-linking of synapsin. These actions might also account for toxin-induced blockade of exocytosis. Therefore, a series of experiments were performed to evaluate the possibility that tetanus toxin exerts its effects via transglutaminase. The results indicated that clostridial neurotoxins were poor substrates for the cross- linking effects of transglutaminase, and transglutaminase was a poor substrate for the proteolytic actions of tetanus toxin. In addition, at concentrations relevant to blockade of exocytosis, clostridial neurotoxins did not act on intact cells to stimulate transglutaminase, nor did they act on the isolated enzyme to stimulate cross-linking of putrescine and dimethylcasein. When used as competitive inhibitors of endogenous transglutaminase substrates, glycine methyl ester and monodansylcadaverine did not block toxin action. Furthermore, concentrations of calcium that were too low to support transglutaminase activity did not prevent toxin action. The data suggest that stimulation of transglutaminase is not the principal mechanism by which tetanus toxin blocks exocytosis in nerve cells.

Original languageEnglish (US)
Pages (from-to)24454-24458
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number39
StatePublished - Sep 30 1994
Externally publishedYes

Fingerprint

Tetanus Toxin
Transglutaminases
Exocytosis
Substrates
R-SNARE Proteins
Synapsins
Putrescine
Synaptic Vesicles
Enzymes
Crosslinking
Neurons
Zinc
Transmitters
Calcium
Membranes
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Coffield, J. A., Considine, R., Jeyapaul, J., Maksymowych, A. B., Zhang, R. D., & Simpson, L. L. (1994). The role of transglutaminase in the mechanism of action of tetanus toxin. Journal of Biological Chemistry, 269(39), 24454-24458.

The role of transglutaminase in the mechanism of action of tetanus toxin. / Coffield, Julie A.; Considine, Robert; Jeyapaul, Janet; Maksymowych, Andrew B.; Zhang, Ren De; Simpson, Lance L.

In: Journal of Biological Chemistry, Vol. 269, No. 39, 30.09.1994, p. 24454-24458.

Research output: Contribution to journalArticle

Coffield, JA, Considine, R, Jeyapaul, J, Maksymowych, AB, Zhang, RD & Simpson, LL 1994, 'The role of transglutaminase in the mechanism of action of tetanus toxin', Journal of Biological Chemistry, vol. 269, no. 39, pp. 24454-24458.
Coffield JA, Considine R, Jeyapaul J, Maksymowych AB, Zhang RD, Simpson LL. The role of transglutaminase in the mechanism of action of tetanus toxin. Journal of Biological Chemistry. 1994 Sep 30;269(39):24454-24458.
Coffield, Julie A. ; Considine, Robert ; Jeyapaul, Janet ; Maksymowych, Andrew B. ; Zhang, Ren De ; Simpson, Lance L. / The role of transglutaminase in the mechanism of action of tetanus toxin. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 39. pp. 24454-24458.
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