Neurotoxin tetanus

The most ingenious exocytosis toxins, however, come from the anaerobic bacteria Clostridium botulinum and Clostridium tetani. The former produces the seven botulinum neurotoxins (BoNTs) A-G the latter produces tetanus neurotoxin (TeNT). All eight toxins consist of a heavy (H) chain and a light (L) chain that are associated by an interchain S-S bond. The L-chains enter the cytosol of axon terminals. Importantly, BoNT L-chains mainly enter peripheral cholinergic terminals, whereas the TeNT L-chain mainly enters cerebral and spinal cord GABAergic and glycinergic terminals. The L-chains are the active domains of the toxins. They are zinc-endopeptidases and specifically split the three core proteins of exocytosis, i.e. the SNAREs (Fig. 1 inset). Each ofthe eight toxins splits a... 

Ledoux, D.N., Be, X.H. and Singh, B.R., Quaternary structure of botulinum and tetanus neurotoxins as probed by chemical cross-linking and native gel electrophoresis, Toxicon, 32, 1095-1104, 1994. 

Schengrund, C.L., Ringler, N.J. and DasGupta, B.R., Adherence of botulinum and tetanus neurotoxins to synaptosomal proteins, Brain Res. Bull., 29, 917-924, 1991. 

The SNAREs involved in the fusion of synaptic vesicles and of secretory granules in neuroendocrine cells, referred to as neuronal SNAREs, have been intensely studied and serve as a paradigm for all SNAREs. They include syntaxin 1A and SNAP-25 at the presynaptic membrane and synaptobrevin 2 (also referred to as VAMP 2) at the vesicle membrane. Their importance for synaptic neurotransmission is documented by the fact that the block in neurotransmitter release caused by botulinum and tetanus neurotoxins is due to proteolysis of the neuronal SNAREs (Schiavo et al. 2000). Genetic deletion of these SNAREs confirmed their essential role in the last steps of neurotransmitter release. Intriguingly, analysis of chromaffin cells from KO mice lacking synaptobrevin or SNAP-25 showed that these proteins can be at least partially substituted by SNAP-23 and cellubrevin, respectively (Sorensen et al. 2003 Borisovska et al. 2005), i.e., the corresponding SNAREs involved in constitutive exocytosis. 

Breidenbach MA, Brunger AT (2005a) 2.3 A crystal structure of tetanus neurotoxin light chain. Biochemistry 44 7450-7... 

Hughes R, Whaler BC (1962) Influence of nerve-ending activity and of drugs on the rate of paralysis of rat diaphragm preparations by cl. botulinum type a toxin. J Physiol 160 221-33 Humeau Y, Doussau F, Grant NJ, Poulain B (2000) How botulinum and tetanus neurotoxins block neurotransmitter release. Biochimie 82 427 16... 

Matteoli M, Verderio C, Rossetto O, Iezzi N, Coco S et al. (1996) Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. Proc Natl Acad Sci U S A 93 13310-15... 

Rossetto O, Caccin P, Rigoni M, Tonello F, Bortoletto N et al. (2001a) Active-site mutagenesis of tetanus neurotoxin implicates tyr-375 and glu-271 in metalloproteolytic activity. Toxicon 39 1151-9... 

Keller A., Sweeney S. T., Zars T., O Kane C. and Heisenberg M. (2002) Targeted expression of tetanus neurotoxin interferes with behavioral responses to sensory input in Drosophila. J. Neurobiol. 50, 221-233. 

TeNT. See Tetanus neurotoxin N-Tert-butyl-(2-sulfophenyal)-nitrone (S-PBN), 417 Tetanus neurotoxin, 266 THC. See Delta-9-tetrahydrocannabinol Thiazolidinediones, 171 3a,5a-THP... 

Alberts P, Rudge R, Hinners I, Muzerelle A, Martinez-Area S, et al. 2003. Cross talk between tetanus neurotoxin-insensitive veside-assodated membrane protein-mediated transport and Ll-mediated adhesion. Mol Biol Cell 14 ... 

Tetanus neurotoxin-insensitive VAMP Tosyl-lysyl chloromethyl ketone Toll-like receptor... 

Tetanus is a syndrome that is often lethal, characterized by a spastic paralysis. Death follows bodily exhaustion and occurs by respiratory failure or circulatory collapse. For twenty four centuries tetanus had been considered a neurologic disease until the identification of Clostridium tefani, the bacterium that causes tetanus by the release of a protein toxin, named tetanus neurotoxin (TeTx)(Faber, 1890 Kitasato, ... 

Matsuda M, Yoneda M (1975) Isolation and purification of two antigenically active, complementary polypeptide fragments of tetanus neurotoxin. In Infect. Immun. 12 1147-53... 

DasGupta BR, editor (1993) Botulinum and tetanus neurotoxins. Plenum Press. New York. 

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