Clostridial neurotoxins as tools to investigate the molecular events of neurotransmitter release.
The clostridial neurotoxins responsible for tetanus and botulism are eight different proteins, composed of two disulfide-linked polypeptide chains. They bind specifically to the presynaptic membrane via the heavy chain, while the light chain enters the cytosol of the neurons, where it displays a zinc-endopeptidase activity directed to proteins of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxin serotypes B, D, F and G cleave specifically and at single different peptide bonds VAMP/synaptobrevin, a component of small synaptic vesicles. In contrast, the other neurotoxins catalyze the hydrolysis of proteins of the presynaptic membrane. Serotypes A and E of botulinum neurotoxin cleave SNAP-25, at different sites located within the carboxyl-terminus, while the specific target of serotype C is syntaxin.
Schiavo
G
G
Dipartimento di Scienze Biomediche, Università di Padova, Italy.
Rossetto
O
O
Montecucco
C
C
D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D003013:Clostridium / Q000737:chemistry; D005089:Exocytosis; D008666:Metalloendopeptidases / Q000378:metabolism; D008967:Molecular Biology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D013744:Tetanus Toxin / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc
D018377:Neurotransmitter Agents; D013744:Tetanus Toxin; D008666:Metalloendopeptidases; D001905:Botulinum Toxins; D015032:Zinc