EXPLORING THE FUNCTIONAL DOMAIN AND THE TARGET OF THE TETANUS TOXIN LIGHT-CHAIN IN NEUROHYPOPHYSEAL TERMINALS

The tetanus toxin light chain blocks calcium induced vasopressin relea se from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zinc binding motif of the tetanus toxi n light chain is essential for the inhibition of exocytosis, in the ra t. The zinc chelating agent dipicolinic acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the n eurotoxin. Synthetic peptides, the sequences of which correspond to mo tifs present in the cytoplasmic domain of the synaptic vesicle membran e protein synaptobrevin I and 2, prevent the effect of the tetanus tox in light chain. Our results indicate that zinc bound to the zinc bindi ng motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that cleavage of synaptobrevin by the neurotoxi n causes the inhibition of exocytotic release of vasopressin from secr etory granules.