Synaptobrevin cleavage by the tetanus toxin light chain is linked to the inhibition of exocytosis in chromaffin cells

Exocytosis of secretory granules by adrenal chromaffin cells is
blocked by the tetanus toxin light chain in a zinc specific manner.
Here we show that cellular synaptobrevin is almost completely
degraded by the tetanus toxin light chain within 15 min. We used
highly purified adrenal secretory granules to show that
synaptobrevin, which can be cleaved by the tetanus toxin light
chain, is localized in the vesicular membrane. Proteolysis of
synaptobrevin in cells and in secretory granules is reversibly
inhibited by the zinc chelating agent dipicolinic acid. Moreover,
cleavage of synaptobrevin present in secretory granules by the
tetanus toxin light chain is blocked by the zinc peptidase
inhibitor captopril and by synaptobrevin derived peptides. Our data
indicate that the tetanus toxin light chain acts as a zinc
dependent protease that cleaves synaptobrevin of secretory
granules, an essential component of the exocytosis machinery in
adrenal chromaffin cells.