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 blocke d 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 adren al secretory granules to show that synaptobrevin, which can be cleaved by the tetanus toxin light chain, is localized in the vesicular membr ane. Proteolysis of synaptobrevin in cells and in secretory granules i s reversibly inhibited by the zinc chelating agent dipicolinic acid. M oreover, cleavage of synaptobrevin present in secretory granules by th e tetanus toxin light chain is blocked by the zinc peptidase inhibitor captopril and by synaptobrevin derived peptides. Our data indicate th at the tetanus toxin light chain acts as a zinc dependent protease tha t cleaves synaptobrevin of secretory granules, an essential component of the exocytosis machinery in adrenal chromaffin cells.