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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)13310-13315
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number23
DOIs
Publication statusPublished - Nov 12 1996

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R-SNARE Proteins
Synaptic Vesicles
Endocytosis
Cytosol
Neurons
Muscle Spasticity
Exocytosis
Tetanus
Paralysis
Synapses
Neurotransmitter Agents
Spinal Cord
tetanospasmin

ASJC Scopus subject areas

  • Genetics
  • General

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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 journalArticle

Matteoli, Michela ; Verderio, Claudia ; Rossetto, Ornella ; Iezzi, Numa ; Coco, Silvia ; Schiavo, Giampietro ; Montecucco, Cesare. / Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 23. pp. 13310-13315.
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