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.