破伤风毒素的作用：与突触小泡蛋白水解相关的神经递质释放抑制。

Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis.

作者信息

Link E, Edelmann L, Chou J H, Binz T, Yamasaki S, Eisel U, Baumert M, Südhof T C, Niemann H, Jahn R

机构信息

Department of Pharmacology, Yale University Medical School, New Haven, CT 06510.

出版信息

Biochem Biophys Res Commun. 1992 Dec 15;189(2):1017-23. doi: 10.1016/0006-291x(92)92305-h.

DOI:10.1016/0006-291x(92)92305-h

PMID:1361727

Abstract

Tetanus toxin is a potent neurotoxin that inhibits the release of neurotransmitters from presynaptic nerve endings. The mature toxin is composed of a heavy and a light chain that are linked via a disulfide bridge. After entry of tetanus toxin into the cytoplasm, the released light chain causes block of neurotransmitter release. Recent evidence suggests that the L-chain may act as a metalloendoprotease. Here we demonstrate that blockade of neurotransmission by tetanus toxin in isolated nerve terminals is associated with a selective proteolysis of synaptobrevin, an integral membrane protein of synaptic vesicles. No other proteins appear to be affected by tetanus toxin. In addition, recombinant light chain selectively cleaves synaptobrevin when incubated with purified synaptic vesicles. Our data suggest that cleavage of synaptobrevin is the molecular mechanism of tetanus toxin action.

摘要

破伤风毒素是一种强效神经毒素，可抑制神经递质从突触前神经末梢释放。成熟毒素由重链和轻链组成，二者通过二硫键相连。破伤风毒素进入细胞质后，释放出的轻链会导致神经递质释放受阻。最近的证据表明，轻链可能作为一种金属内蛋白酶发挥作用。在此我们证明，破伤风毒素在离体神经末梢中对神经传递的阻断与突触小泡膜整合蛋白突触小泡蛋白的选择性蛋白水解有关。似乎没有其他蛋白质受破伤风毒素影响。此外，重组轻链与纯化的突触小泡一起孵育时可选择性切割突触小泡蛋白。我们的数据表明，突触小泡蛋白的切割是破伤风毒素作用的分子机制。