Poulain B
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif-sur-yvette, France.
Pathol Biol (Paris). 1994 Feb;42(2):173-82.
Tetanus toxin and botulinum neurotoxins are di-chain proteins of 150 kD molecular weight. They are produced by bacteria of the Clostridium genus. These toxins act on the nervous system by inhibiting neurotransmitter release (glycine and GABA in the case of tetanus toxin; acetylcholine in the case of botulinum neurotoxins) thus inducing the spastic or flaccid paralysis that characterizes tetanus and botulism, respectively. Their cellular mechanism of action involves three main steps, namely binding to the neurone membrane, internalization and intracellular blockade of the release mechanism for neurotransmitters. Membrane acceptors for these toxins are not yet fully identified; they would consist of membrane gangliosides and proteins. The internalization step would be achieved by endocytosis. Recent findings show that both binding and internalization are mediated only by the heavy chain of the toxins whereas the intracellular blockade of neurotransmitter release involves their light chain alone. The light chain has been identified as a zinc metalloprotease and its substrates would be proteins involved in the neurotransmitter release mechanism. The target of tetanus toxin and of botulinum neurotoxin type B is VAMP/synaptobrevin, a membrane protein of the synaptic vesicles of nerve cell terminals.
破伤风毒素和肉毒杆菌神经毒素是分子量为150kD的双链蛋白质。它们由梭菌属细菌产生。这些毒素通过抑制神经递质释放（破伤风毒素作用于甘氨酸和γ-氨基丁酸；肉毒杆菌神经毒素作用于乙酰胆碱）来作用于神经系统，从而分别诱发破伤风和肉毒中毒所特有的痉挛性或弛缓性麻痹。它们的细胞作用机制涉及三个主要步骤，即与神经元膜结合、内化以及细胞内对神经递质释放机制的阻断。这些毒素的膜受体尚未完全确定；它们可能由膜神经节苷脂和蛋白质组成。内化步骤将通过胞吞作用实现。最近的研究结果表明，结合和内化仅由毒素的重链介导，而细胞内对神经递质释放的阻断仅涉及它们的轻链。轻链已被鉴定为一种锌金属蛋白酶，其底物可能是参与神经递质释放机制的蛋白质。破伤风毒素和B型肉毒杆菌神经毒素的作用靶点是VAMP/突触小泡蛋白，它是神经细胞终末突触小泡的一种膜蛋白。
