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Dissecting the L Chains of Clostridial Neurotoxins

  • Heiner Niemann
  • Thomas Binz
  • Oliver Grebenstein
  • Hisao Kurazono
  • Arno Kalkuhl
  • Shinji Yamasaki
  • Ulrich Eisel
  • Johannes Pohlner
  • Germar Schneider
  • Viliam Krivan
  • Shunji Kozaki
  • Sumiko Mochida
  • Ladislav Tauc
  • Bernard Poulain

Abstract

Tetanus toxin (TeTx) and the seven structurally related but serologically distinct botulinal neurotoxins, designated BoNT/A to BoNT/G, bind selectively to nerve terminals where they are internalized and sorted by unknown mechanisms. It is generally accepted that toxification is preceeded by a translocation of the L chains from an acid vesicular environment into the cytosole (Niemann, 1991). Despite such homologies, however, the individual toxins display differences in their primary sites of action, their uptake mechanisms (Poulain et al., 1992) and sensitivity to chemical antagonists (Dreyer et al., 1987; Dolly et al., 1990). We have to assume, therefore, that some of the neurotoxins act on different intracellular targets which appear to play key roles in neurotransmitter release from small translucent as well as large dense-core vesicles. Although tetanus patients immediately receive high doses of human tetanus immune globulin to block any nonbound toxin, the internalized toxin evokes its toxic effects for several weeks (Bleck, 1989). This suggests that the toxins act as enzymes. Several enzymatic activities have been proposed over the past years all of which, however, proved to be wrong later on (Niemann, 1991).

Keywords

Botulinal Toxin Botulinum Neurotoxin Tetanus Toxin Clostridium Botulinum Isoelectric Focussing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ahnert-Hilger, G., Weller, U., Dauzenroth, M.-E., Habermann, E., and Gratzl, M., 1989, The tetanus toxin light chain inhibits exocytosis, FEBS Lett. 242: 245.PubMedCrossRefGoogle Scholar
  2. Bhattacharyya, S.D. and Sugiyama, H., 1989, Inactivation of botulinum and tetanus toxin by chelators, Infect. Immun. 57: 3053.PubMedGoogle Scholar
  3. Binz, T., Kurazono, H., Wille, M., Frevert, J., Wernars, K., and Niemann, H., 1990a, The complete sequence of botulinum toxin type A and comparison with other clostridial neurotoxins, J. Biol. Chem. 265: 9153.PubMedGoogle Scholar
  4. Binz, T., Kurazono, H., Popoff, M., Eklund, M.W., Sakaguchi, G., Kozaki, S., Krieglstein, K., Henschen, A., Gill, D.M., and Niemann, H., 1990b, Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin type D, Nucl. Acids Res. 18: 5556.PubMedCrossRefGoogle Scholar
  5. Bittner, M.A., Habig, W.H., and Holz, R.W., 1989, Isolated light chains of botulinum neurotoxins inhibit exocytosis, J. Biol. Chem. 264: 10354.PubMedGoogle Scholar
  6. Bleck, T.P., 1989, Clinical aspects of tetanus, in: Botulinum Neurotoxin and Tetanus Toxin, L.L. Simpson, ed., Academic Press, San Diego.Google Scholar
  7. Chang, P.-C., and Lee, Y.-. W., 1992, Extracellular autoprocessing of a metalloprotease from Streptomyces cacaoi, J.Biol. Chem. 267: 3952.PubMedGoogle Scholar
  8. DasGupta, B.R. and Rasmussen, S., 1984, Effect of diethylpyrocarbonate on the biological activities of botulinum neurotoxin types A and E, Arch. Biochem. Biophys. 232: 172.PubMedCrossRefGoogle Scholar
  9. Dolly, J.O., Ashton, A.C., McInnes, C., Wadsworth, J.D.F. Poulain, B., Tauc, L., Shone, C.C., and Melling, J., 1990, Clues to the multiphase inhibitory action of botulinum neurotoxins on release of transmitters, J. Physiol. (Paris) 84: 237.Google Scholar
  10. Dreyer, F., Rosenberg, F., Becker, C., Bigalke, H.,and Penner, R., 1987, Differential effects of various secretagogues on quantal transmitter release from mouse nerve terminals treated with botulinum A and tetanus toxin. Naunyn Schmiedeberg’s Arch. of Pharmacol. 335: 1.Google Scholar
  11. Eisel, U., Jarausch, W., Goretzki, K., Henschen, A., Engels, J., Weller, U., Hudel, M., Habermann, E., and Niemann, H., 1986, Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins, EMBO J. 5: 2495.Google Scholar
  12. Hauser, D., Eklund, M.W., Kurazono, H., Binz, T., Niemann, H., Gill, D.M., Boquet, P., and Popoff, M.R., 1990, Nucleotide sequence of Clostridium botulinum Cl neurotoxin, Nucl. Acids Res. 18: 4924.PubMedCrossRefGoogle Scholar
  13. Hochuli, E., Döbeli, H., and Schacher, A., 1987, New metal chelate adsorbents selective for proteins and peptide containing neighbouring histidine residues. J. Chromatography 411: 177.CrossRefGoogle Scholar
  14. Holmes, M.A. and Matthews, B.W., 1982, Structure of thermolysin at 1,6 A resolution, J. Mol. Biol. 160: 623.PubMedCrossRefGoogle Scholar
  15. Kozaki, S., Mild, A., Kamata, Y., Ogasawara, J., and Sakaguchi, G., 1989, Immunological characterization of papain-induced fragments of clostridium botulinum type A neurotoxin and interaction of the fragments with brain synaptosomes, Infect. Immun. 57: 2634.PubMedGoogle Scholar
  16. Kurazono, H., Mochida, S., Binz, T., Eisel, U., Quanz, M., Grebenstein, O., Poulain, B., Tauc, L., and Niemann, H., 1992a, Minimal essential domains specifying toxicity of the light chains of tetanus toxin and botulinum neurotoxin type A, J. Biol. Chem.,in press.Google Scholar
  17. Kurazono, S., Kozaki, S., Binz, T., Grebenstein, O., and Niemann, H., 1992b, Monoclonal antibodies as tools to dissect the L chains of clostridial neurotoxins, manuscript n preparation.Google Scholar
  18. McInnes, C. and Dolly, J.O., 1990, Cat+-dependent noradrenaline release from permeabilized PC12 cells is blocked by botulinum neurotoxin A or its light chain, FEBS Lett. 261: 323.PubMedCrossRefGoogle Scholar
  19. Mochida, S., Poulain, B., Eisel, U., Binz, T., Kurazono, H., Niemann, H., and Tauc, L., 1990, Exogenous mRNA encoding tetanus or botulinum neurotoxins expressed in Aplysia neurons, Proc. Natl. Acad. Sci. USA 87: 7844.PubMedCrossRefGoogle Scholar
  20. Niemann, H., 1991, Molecular biology of clostridial neurotoxins. in: Sourcebook of Bacterial Protein Toxins, Alouf, J. and Freer, J. eds., pp 303–348. Academic Press, New York.Google Scholar
  21. Penner, R., Neher, E., and Dreyer, F., 1986, Intracellularly injected tetanus toxin inhibits exocytosis in bovine adrenal chromaffin cells, Nature 324: 76.PubMedCrossRefGoogle Scholar
  22. Pohlner, J., Halter, R., Beyreuther, K., and Meyer, T., 1987, Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease, Nature, 325: 458.PubMedCrossRefGoogle Scholar
  23. Poulain, B., Tauc, L.,Maisey, E.A., Wadsworth, J.D:F., Mohan, P.M., and Dolly, J.O., 1988, Neurotransmitter release is blocked intracellularly by botulinum toxin, and this requires both polypeptides by a process mediated by the larger chain. Proc. Natl. Acad. Sci. USA 85: 4090.Google Scholar
  24. Poulain, B., Wadsworth, J.D.F., Shone, C.C., Mochida, S., Lande, S., Melling, J., Dolly, J.O., and Tauc, L., 1989, Multiple domains of botulinum neurotoxin contribute to its inhibition of transmitter release in Aplysia neurons, J. Biol. Chem. 264: 2 1928.Google Scholar
  25. Poulain, B., Paiva, A., Dolly, J.O., Weller, U., and Tauc. L., 1992, Differences in the temperature dependencies of uptake of botulinum and tetanus toxins in Aplysia neurons. Neuroscience Letters 139: 289.PubMedCrossRefGoogle Scholar
  26. Poulet, S., Hauser, D., Quanz, M., Niemann, H., and Popoff, M.R., 1992, Sequences of the botulinal neurotoxin E derived from Clostridium botulinum type E (strain Beluga) and Clostridium butyricum (strains ATCC43181 and ATCC43755). Biochem. Biophys. Res. Commun. 183: 107.Google Scholar
  27. Stecher, B., Weller, U., Habermann, E., Gratzl, M., and Ahnert-Hilger, G., 1989, The light chain but not the heavy chain of botulinum A toxin inhibits exocytosis from permeabilized adrenal chromaffin cells, FEBS Lett. 255: 391.PubMedCrossRefGoogle Scholar
  28. Weller, U., Dauzenroth, M.-E., Meyer zu Heringdorf, D., and Habermann, E., 1989, Chains and fragments of tetanus toxin, Eur. J. Biochem. 182: 649.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Heiner Niemann
    • 1
  • Thomas Binz
    • 1
  • Oliver Grebenstein
    • 1
  • Hisao Kurazono
    • 1
  • Arno Kalkuhl
    • 1
  • Shinji Yamasaki
    • 1
  • Ulrich Eisel
    • 1
  • Johannes Pohlner
    • 2
  • Germar Schneider
    • 3
  • Viliam Krivan
    • 3
  • Shunji Kozaki
    • 4
  • Sumiko Mochida
    • 5
  • Ladislav Tauc
    • 5
  • Bernard Poulain
    • 5
  1. 1.Department of MicrobiologyFederal Research Centre of Virus Diseases of AnimalsTübingenGermany
  2. 2.Max-Planck-Institute for BiologyTübingenGermany
  3. 3.Analytik und HöchstreinigungUniversität UlmUlmGermany
  4. 4.College of AgricultureOsaka Prefecture UniversityMozuumemachi, Sakai, OsakaJapan
  5. 5.Laboratoire de Neurobiologie Cellulaire et MoléculaireCNRSGif-sur-YvetteFrance

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