Endocytosis of Clostridium botulinum type B neurotoxin into rat brain synaptosomes.
Clostridium botulinum type B neurotoxin cleaves VAMP (vesicle-associated membrane protein)/synaptobrevin into two fragments, which results in inhibition of neurotransmitter release. The induced fragment did not react to the antibody raised against the synthetic peptide of the amino-terminal 20 residues of VAMP-2, suggesting that the toxin treatment has caused antigenical alteration in the amino-terminal region of VAMP-2. In rat brain synaptosomes, type B neurotoxin was reduced presumably with sulfhydryls in the membrane and detected in the synaptic vesicle fraction which involved the degradation of VAMP-2 and the inhibition of neurotransmitter release. The light chain in a free form was present in the cytosol fraction. These findings suggest a possibility that type B neurotoxin endocytoses into synaptic vesicles by the recycling pathway and the light chain is penetrable through synaptic vesicle membrane. However, the amount of type B neurotoxin entrapped into synaptic vesicles appears to be extremely small, which may be attributed to a lower sensitivity of the toxin to brain synaptosomes than to peripheral nerve endings.
Kohda
T
T
Laboratories of Veterinary Public Health, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Japan.
Kamata
Y
Y
Kozaki
S
S
D000818:Animals; D001905:Botulinum Toxins / Q000493:pharmacokinetics* / Q000633:toxicity; D001921:Brain / Q000378:metabolism*; D004705:Endocytosis; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000493:pharmacokinetics* / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism; D050683:R-SNARE Proteins; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D050683:R-SNARE Proteins; D001905:Botulinum Toxins; D009638:Norepinephrine