Molecular aspects of tetanus and botulinum neurotoxin poisoning.
Clostridial neurotoxins, tetanus and the botulinum toxins A-G, are high molecular weight proteins consisting of a heavy chain which is responsible for the internalisation and a light chain possessing a zinc-dependent proteolytic activity. They exclusively proteolyse either the vesicle 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 their cleavage blocks the latter process. Clostridial neurotoxins have now become powerful tools to investigate the final events occurring during secretion in neuronal, endocrine, and non-neuronal cells. They are applied to dissect the specific interactions of the SNARE protein complex with cytosolic fusogens and other modulators of exocytosis. Whereas exocytosis is not essential for the survival of cells, the organism as a whole will fall victim to a few nanograms since interneuronal and neuromuscular transmission is vital to muscular control, especially in respiration. Although all clostridial neurotoxins by their light chains attack proteins of the SNARE complex, tetanus toxin and the various botulinum toxins differ dramatically in their clinical symptoms. The biological information for this difference resides on the respective heavy chains which select different transport routes carrying the light chain from the place of entrance to the final compartment of action. So far the different transport vesicles used either by the various botulinum neurotoxins or by tetanus toxin are not yet defined. Nevertheless at least one of the botulinum toxins serves as a beneficial drug in the treatment of severe neuromuscular spasms.
Ahnert-Hilger
G
G
Freie Universität Berlin Universitätsklinikum Benjamin Franklin, Abteilung Gastroenterologie, Germany.
Bigalke
H
H
D001905:Botulinum Toxins; D007700:Kinetics; D008970:Molecular Weight; D013744:Tetanus Toxin
D013744:Tetanus Toxin; D001905:Botulinum Toxins