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PMID: 8917587 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 23 ·1996-11-12 ·Pages 13310-5

Matteoli M, Verderio C, Rossetto O, Iezzi N, Coco S, Schiavo G, Montecucco C

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.

MeSH Terms
Animals Anti-Bacterial Agents/pharmacology Cells, Cultured Cytosol/metabolism Endocytosis Enzyme Inhibitors/pharmacology Fetus Hippocampus/physiology Immunohistochemistry Macrolides Membrane Proteins/metabolism Microscopy, Immunoelectron Nerve Endings/physiology,ultrastructure Neurons/cytology,physiology Neurotoxins/metabolism R-SNARE Proteins Rats Synaptic Vesicles/drug effects,physiology,ultrastructure Tetanus Toxin/metabolism Transferrin/metabolism
Chemicals
Anti-Bacterial Agents Enzyme Inhibitors Macrolides Membrane Proteins Neurotoxins R-SNARE Proteins Tetanus Toxin Transferrin bafilomycin A1
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Matteoli M
Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology, University of Milan, Italy. MichelaM@farma.csfic.mi.cnr.it
Verderio C
Rossetto O
Iezzi N
Coco S
Schiavo G
Montecucco C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.23.13310
Email
michelam@farma.csfic.mi.cnr.it
Published
1996-11-12
Pages
13310-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24089
Subset
IM
Grants
Telethon · 672 · Italy
Telethon · 763 · Italy
External Links
PubMed source DOI: 10.1073/pnas.93.23.13310 PMC Full Text View journal details
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