title: Synaptobrevin cleavage by the tetanus toxin light chain is linked to the inhibition of exocytosis in chromaffin cells.
abstract: 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.
authors.affiliation: Abteilung Anatomie und Zellbiologie der Universität, Ulm, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Höhne-Zell
authors.forename: A
authors.initials: A
authors.lastname: Ecker
authors.forename: U
authors.initials: U
authors.lastname: Weller
authors.forename: M
authors.initials: M
authors.lastname: Gratzl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002837:Chromaffin Granules / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050683:R-SNARE Proteins; D013744:Tetanus Toxin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D050683:R-SNARE Proteins; D013744:Tetanus Toxin