Poisoning by botulinum neurotoxin A does not inhibit formation or disassembly of the synaptosomal fusion complex.
We investigated the effect of poisoning rat brain synaptosomes with botulinum neurotoxin A on the NSF-mediated disassembly of a complex consisting of syntaxin, SNAP-25 and synaptobrevin (fusion complex). Botulinum neurotoxin A specifically removes 9 amino acids from the C-terminus of SNAP-25 and efficiently blocks KCl-evoked glutamate release from synaptosomes. We report that truncated SNAP-25 is incorporated into the fusion complex of poisoned synaptosomes. The presence of truncated SNAP-25 does not interfere with the NSF-induced disassembly of the fusion complex. Also, the release of truncated SNAP-25 from the fusion complex is similar to that of the native SNAP-25. Since neither the formation of the complex nor its disassembly seems to be affected by the SNAP-25 fragment, this fragment is likely to block exocytosis by disrupting events between disassembly of the synaptosomal fusion complex and membrane fusion itself.
Otto
H
H
Howard Hughes Medical Institute, Yale University Medical School, New Haven, CT 06510, USA.
Hanson
P I
PI
Chapman
E R
ER
Blasi
J
J
Jahn
R
R
D000818:Animals; D001905:Botulinum Toxins / Q000506:poisoning*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008561:Membrane Fusion / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051381:Rats; D050825:Synaptosomal-Associated Protein 25; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D018698:Glutamic Acid; D001905:Botulinum Toxins