Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum a toxin

Habermann, E.; Dreyer, Florian; Bigalke, Hans

doi:10.1007/bf00500299

Cited by 131 publications

(55 citation statements)

References 28 publications

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“…ACh release from the neuromuscular junction is blocked by TeTx [6,7] and, as it has been shown in this paper, the K+-induced release of ACh from isolated cholinergic synaptosomes is also inhibited by TeTx. BoTx, another neurotoxin produced by related microorganisms (C. botulinum), that acts specifically at the cholinergic synapse (see [16] as a review), also reduces ACh release from the isolated cholinergic synaptosomes [lo].…”

Section: Discussion Acknowledgementssupporting

confidence: 60%

“…As we have mentioned, TeTx inhibits ACh release from neuromuscular junction [6]. Here we have assayed the ability of this toxin to inhibit ACh release from pure cholinergic synaptosomes isolated from the electric organ of Torpedo.…”

Section: Ach Releasementioning

confidence: 99%

“…Both, ATP and ACh release are calcium dependent processes [4]. TeTx, an exotoxin produced by ~~os~~~~~urn tetani, impairs neurotransmitter release from several different neurotransmitter systems (review 151) and, also, like botulinum toxin type A (BoTx), another clostridial toxin, blocks neuromuscular transmission by blocking ACh release [6,7]. The electric organ of Torpedo marmorata is a modified neuromuscular system, in which presynaptic nerve terminals are highly ACh, acetylcholine; BoTx, botu~~um toxin; TeTx, tetanus toxin multiplied [8], From this tissue, a fraction of pure cholinergic nerve endings can be obtained [9], which are a suitable model to study ACh and ATP co-release.…”

Section: Introductionmentioning

confidence: 99%

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ATP release from pure cholinergic synaptosomes is not blocked by tetanus toxin

et al. 1987

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Tetanus toxin (TeTx) is a neurotransmission impairing toxin that acts on several neurotransmitter systems. TeTx also inhibits the K+-induced release of acetylcholine (ACh) from synaptosomes isolated from the electric organ of Torpedo. Neither the membrane potential and depolarization, nor the depolarization-induced calcium uptake into cholinergic nerve terminals is modified after TeTx poisoning. On the other hand, it is known that, when cholinergic nerve terminals are stimulated, there is a release of ATP associated with the release of ACh. We have explored the action of TeTx on this co-release, and have found that there is no action of TeTx on the nucleotide release. Thus, TeTx blocks ACh release without modifying ATP release.

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Section: Discussion Acknowledgementssupporting

confidence: 60%

Section: Ach Releasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ATP release from pure cholinergic synaptosomes is not blocked by tetanus toxin

et al. 1987

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“…The mouse phrenic nerve toxicity assay was set up, as described by Habermann et al (39) and Wohlfarth et al (40). Electrical stimulation of the phrenic nerve was continuously performed at a frequency of 1 Hz.…”

Section: Experimental Procedures Molecularmentioning

confidence: 99%

Identification of the protein receptor binding site of botulinum neurotoxins B and G proves the double-receptor concept

Rummel

Eichner

Weil

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

171

216

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Botulinum neurotoxins (BoNTs) cause muscle paralysis by selectively cleaving core components of the vesicular fusion machinery within motoneurons. Complex gangliosides initially bind into a pocket that is conserved among the seven BoNTs and tetanus neurotoxin. Productive neurotoxin uptake also requires protein receptors. The interaction site of the protein receptor within the neurotoxin is currently unknown. We report the identification and characterization of the protein receptor binding site of BoNT/B and BoNT/G. Their protein receptors, synaptotagmins I and II, bind to a pocket at the tip of their HCC (C-terminal domain of the C-terminal fragment of the heavy chain) that corresponds to the unique second carbohydrate binding site of tetanus neurotoxin, the sialic acid binding site. Substitution of amino acids in this region impaired binding to synaptotagmins and drastically decreased toxicity at mouse phrenic nerve preparations; CD-spectroscopic analyses evidenced that the secondary structure of the mutated neurotoxins was unaltered. Deactivation of the synaptotagmin binding site by single mutations led to virtually inactive BoNT/B and BoNT/G when assayed at phrenic nerve preparations of complex-ganglioside-deficient mice. Analogously, a BoNT B mutant with deactivated ganglioside and synaptotagmin binding sites lacked appreciable activity at wild-type mouse phrenic nerve preparations. Thus, these data exclude relevant contributions of any cell surface molecule other than one ganglioside and one protein receptor to the entry process of BoNTs, which substantiates the double-receptor concept. The molecular characterization of the synaptotagmin binding site provides the basis for designing a novel class of potent binding inhibitors.synaptotagmin ͉ tetanus B otulinum neurotoxins (BoNTs) (serotypes A-G) are the causative agents of the disease botulism. The neurotoxins are produced as Ϸ150-kDa single-chain proteins in Clostridium botulinum and subsequently cleaved by proteases, yielding an Ϸ100-kDa heavy chain (HC) and an Ϸ50-kDa light chain (LC). These chains remain connected via a single disulfide bridge, noncovalent interactions, and a HC-derived peptide loop wrapped around the LC. The LCs act as zinc metallopeptidases, which solely hydrolyze one of three SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) proteins: vesicle associated membrane protein/synaptobrevin, synaptosomal-associated protein of 25 kDa, or syntaxin. Together, these substrate molecules constitute the core of the vesicular fusion machinery. Thus, cleavage of one of these proteins inhibits the release of neurotransmitters from synaptic vesicles into the synaptic cleft. The HCs mediate the neurospecific binding, uptake by receptor-mediated endocytosis, and transport of the LC across the endosomal membrane into the cytosol, where the LCs encounter their substrates. The Ϸ50-kDa

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“…The spastic paralysis induced by the toxin is due to the blockade of neurotransmitter release from spinal inhibitory neurons (Pellizzari et al, 1999). On the other hand, tetanus toxin blocks neuromuscular transmission by inhibiting the release of neurotransmitters from motor nerve terminals and thereby causes flaccid paralysis (Habermann et al, 1980). Botulinum neurotoxin produced by C. botulinum, another clostridial neurotoxin, has a similar action and causes botulism in human (Pellizzari et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

A mechanism of the thearubigin fraction of black tea (camellia sinensis) extract protecting against the effect of tetanus toxin.

et al. 2002

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-The aim of the present study was to elucidate the mechanism of the protective effect of black tea extract's thearubigin fraction against the action of tetanus toxin. The effects of thearubigin fraction extracted from a black tea infusion were examined for neuromuscular blocking action on tetanus toxin in mouse phrenic nerve-diaphragm preparations and on the binding of this toxin to the synaptosomal membrane preparations of rat cerebral cortices. The interaction between tetanus toxin and thearubigin fraction was also investigated. Tetanus toxin (4 µg/ml) abolished indirect twitches in mouse phrenic nerve-diaphragm preparations within 150 min. Thearubigin fraction mixed with tetanus toxin blocked the inhibitory effect of the toxin. Mixing iodinated toxin with thearubigin fraction inhibited the specific binding of [

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Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum a toxin

Cited by 131 publications

References 28 publications

ATP release from pure cholinergic synaptosomes is not blocked by tetanus toxin

ATP release from pure cholinergic synaptosomes is not blocked by tetanus toxin

Identification of the protein receptor binding site of botulinum neurotoxins B and G proves the double-receptor concept

A mechanism of the thearubigin fraction of black tea (camellia sinensis) extract protecting against the effect of tetanus toxin.

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