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

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

doi:10.1073/pnas.93.23.13310

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

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

Istituto Clinico Humanitas

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	13310-13315
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	93
Issue number	23
DOIs	https://doi.org/10.1073/pnas.93.23.13310
Publication status	Published - Nov 12 1996

ASJC Scopus subject areas

Genetics
General

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10.1073/pnas.93.23.13310

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Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. / Matteoli, Michela; Verderio, Claudia; Rossetto, Ornella; Iezzi, Numa; Coco, Silvia; Schiavo, Giampietro; Montecucco, Cesare.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 23, 12.11.1996, p. 13310-13315.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Coco, Silvia

AU - Schiavo, Giampietro

AU - Montecucco, Cesare

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AB - 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.

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

Abstract

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