Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals.
The tetanus toxin light chain blocks calcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zinc binding motif of the tetanus toxin light chain is essential for the inhibition of exocytosis, in the rat. The zinc chelating agent dipicolinic acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesicle membrane protein synaptobrevin 1 and 2, prevent the effect of the tetanus toxin light chain. Our results indicate that zinc bound to the zinc binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that cleavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules.
Dayanithi
G
G
Laboratoire de Neurobiologie Endocrinologique URA 1197, CNRS, Université Montpellier-2, France.
Stecher
B
B
Höhne-Zell
B
B
Yamasaki
S
S
Binz
T
T
Weller
U
U
Niemann
H
H
Gratzl
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009411:Nerve Endings / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010848:Picolinic Acids / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000293:injuries*; D050683:R-SNARE Proteins; D051381:Rats; D017208:Rats, Wistar; D013301:Streptolysins / Q000494:pharmacology; D016704:Synapsins / Q000187:drug effects / Q000378:metabolism; D013744:Tetanus Toxin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D014667:Vasopressins / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010848:Picolinic Acids; D050683:R-SNARE Proteins; D013301:Streptolysins; D016704:Synapsins; D013744:Tetanus Toxin; C025964:streptolysin O; D014667:Vasopressins; D002216:Captopril; D001905:Botulinum Toxins; D015032:Zinc