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

1996; National Academy of Sciences; Volume: 93; Issue: 23 Linguagem: Inglês

10.1073/pnas.93.23.13310

1091-6490

Michela Matteoli, Claudia Verderio, Ornella Rossetto, Numa Iezzi, Silvia Coco, Giampietro Schiavo, Cesare Montecucco,

Lipid Membrane Structure and Behavior

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.