Involvement of the constituent chains of botulinum neurotoxins A and B in the blockade of neurotransmitter release - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Biochemistry Année : 1988

Involvement of the constituent chains of botulinum neurotoxins A and B in the blockade of neurotransmitter release

E. Anne Maisey
  • Fonction : Auteur
Jonathan D. F. Wadsworth
  • Fonction : Auteur
Clifford C. Shone
  • Fonction : Auteur
Jack Melling
  • Fonction : Auteur
Paul Gibbs
  • Fonction : Auteur
Ladislav Tauc
  • Fonction : Auteur
J. Oliver Dolly
  • Fonction : Auteur

Résumé

1. The abilities of botulinum neurotoxins, types A and B (single and two‐chain forms) to inactivate an intraneuronal component required for transmitter release were quantified in a phrenic‐nerve‐diaphragm preparation, cerebrocortical synaptosomes or the buccal ganglion of Aplysia californica and compared with the mouse toxicity assay. 2. Homogeneous preparations of the individually renatured polypeptide chains of both toxin types showed low residual toxicity in the whole animal and had no effect on neurotransmission in all three systems, when tested singly. 3. Mixtures of individually renatured heavy chain, from type A or B, and either light chain proved very effective in blocking the evoked release of acetylcholine when bath‐applied to the buccal ganglion of Aplysia whilst they were relatively inactive on mammalian nerve terminals, indicating a less efficient uptake of the polypeptides in the latter. 4. When renatured together, the homologous, but not the heterologous, chains of each toxin type yielded toxic, disulphide‐linked two‐chain species. 5. A role for the heavy chain alone in acceptor recognition and membrane translocation was implicated by the blockade of acetylcholine release produced when light chain was applied to a ganglion of Aplysia previously bathed in heavy chain and washed extensively. No blockade was observed when the order of application of the two chains was reversed. 6.These findings are discussed in the context of the intracellular requirement for both the constituent toxin chains for toxicity, and in the apparent need for these chains to be linked via a disulphide bond for uptake in rodents but not in Aplysia.

Domaines

Toxicologie

Dates et versions

hal-03150662 , version 1 (23-02-2021)

Identifiants

Citer

E. Anne Maisey, Jonathan D. F. Wadsworth, Bernard Poulain, Clifford C. Shone, Jack Melling, et al.. Involvement of the constituent chains of botulinum neurotoxins A and B in the blockade of neurotransmitter release. European Journal of Biochemistry, 1988, 177 (3), pp.683-691. ⟨10.1111/j.1432-1033.1988.tb14423.x⟩. ⟨hal-03150662⟩

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