Höhne-Zell B, Ecker A, Weller U, Gratzl M
Abteilung Anatomie und Zellbiologie der Universität, Ulm, Germany.
FEBS Lett. 1994 Nov 28;355(2):131-4. doi: 10.1016/0014-5793(94)01192-3.
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.
破伤风毒素轻链以锌特异性方式阻断肾上腺嗜铬细胞分泌颗粒的胞吐作用。在此我们表明，细胞中的突触囊泡蛋白在15分钟内几乎被破伤风毒素轻链完全降解。我们使用高度纯化的肾上腺分泌颗粒来表明，可被破伤风毒素轻链切割的突触囊泡蛋白定位于囊泡膜中。锌螯合剂吡啶二羧酸可可逆地抑制细胞和分泌颗粒中突触囊泡蛋白的蛋白水解作用。此外，锌肽酶抑制剂卡托普利和突触囊泡蛋白衍生肽可阻断破伤风毒素轻链对分泌颗粒中突触囊泡蛋白的切割。我们的数据表明，破伤风毒素轻链作为一种锌依赖性蛋白酶，可切割分泌颗粒的突触囊泡蛋白，而突触囊泡蛋白是肾上腺嗜铬细胞胞吐机制的重要组成部分。
