MOLECULAR ASPECTS OF TETANUS AND BOTULINUM NEUROTOXIN POISONING

Clostridial neurotoxins, tetanus and the botulinum toxins A-G, are hig h molecular weight proteins consisting of a heavy chain which is respo nsible for the internalisation and a light chain possessing a zinc-dep endent proteolytic activity. They exclusively proteolyse either the ve sicle membrane protein, synaptobrevin or two integral plasma membrane proteins, SNAP 25 and syntaxin. Together with cytosolic proteins these proteins form the SNARE complex involved in vesicle exocytosis, and t heir cleavage blocks the latter process. Clostridial neurotoxins have now become powerful tools to investigate the final events occurring du ring secretion in neuronal, endocrine, and non-neuronal cells. They ar e applied to dissect the specific interactions of the SNARE protein co mplex with cytosolic fusogens and other modulators of exocytosis. Wher eas exocytosis is not essential for the survival of cells, the organis m as a whole will fall victim to a few nanograms since interneuronal a nd neuromuscular transmission is vital to muscular control, especially in respiration. Although all clostridial neurotoxins by their light c hains attack proteins of the SNARE complex, tetanus toxin and the vari ous botulinum toxins differ dramatically in their clinical symptoms. T he biological information for this difference resides on the respectiv e heavy chains which select different transport routes carrying the li ght chain from the place of entrance to the final compartment of actio n, So far the different transport vesicles used either by the various botulinum neurotoxins or by tetanus toxin are not yet defined. Neverth eless at least one of the botulinum toxins serves as a beneficial drug in the treatment of severe neuromuscular spasms.