Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons

Tetanus neurotoxin causes the spastic paralysis of tetanus by blocking neurotransmitter release at inhibitory synapses of the spinal cord. This is due to the penetration of the toxin inside the neuronal cytosol where it cleaves specifically VAMP/synaptobrevin, an essential component of the neuroexocytosis apparatus. Here we show that tetanus neurotoxin is internalized inside the lumen of small synaptic vesicles following the process of vesicle reuptake. Vesicle acidification is essential for the toxin translocation in the cytosol, which results in the proteolytic cleavage of VAMP/synaptobrevin and block of exocytosis.

破伤风神经毒素（Tetanus neurotoxin）可通过阻断脊髓抑制性突触处的神经递质释放，引发破伤风的痉挛性麻痹。该毒素的致病机制为：其穿透进入神经元胞质后，会特异性切割囊泡相关膜蛋白/突触泡蛋白（VAMP/synaptobrevin）——神经分泌装置的必需组分。本研究发现，破伤风神经毒素可通过囊泡再摄取过程，被内吞至小型突触囊泡的管腔中。囊泡酸化对于毒素向胞质的转位不可或缺，该转位过程最终会导致VAMP/synaptobrevin的蛋白水解切割，并阻断胞吐作用。