Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons.
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.
Matteoli
M
M
Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology, University of Milan, Italy. MichelaM@farma.csfic.mi.cnr.it
Verderio
C
C
Rossetto
O
O
Iezzi
N
N
Coco
S
S
Schiavo
G
G
Montecucco
C
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D018942:Macrolides; D008565:Membrane Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D009411:Nerve Endings / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009498:Neurotoxins / Q000378:metabolism*; D050683:R-SNARE Proteins; D051381:Rats; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013744:Tetanus Toxin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D008565:Membrane Proteins; D009498:Neurotoxins; D050683:R-SNARE Proteins; D013744:Tetanus Toxin; D014168:Transferrin; C040929:bafilomycin A1