突触小泡内吞作用介导破伤风神经毒素进入海马神经元。
Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons.
作者信息
Matteoli M, Verderio C, Rossetto O, Iezzi N, Coco S, Schiavo G, Montecucco C
机构信息
Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology, University of Milan, Italy.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13310-5. doi: 10.1073/pnas.93.23.13310.
Abstract
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.
摘要
破伤风神经毒素通过阻断脊髓抑制性突触处的神经递质释放，导致破伤风的痉挛性麻痹。这是由于毒素穿透神经元胞质溶胶，在其中特异性切割VAMP/突触囊泡蛋白，而VAMP/突触囊泡蛋白是神经外排装置的重要组成部分。在此我们表明，破伤风神经毒素在小突触囊泡再摄取过程中被内化到囊泡腔内。囊泡酸化对于毒素在胞质溶胶中的转运至关重要，这会导致VAMP/突触囊泡蛋白的蛋白水解切割并阻断胞吐作用。
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