Insights into a basis for incomplete inhibition by botulinum toxin A of Ca2+-evoked exocytosis from permeabilised chromaffin cells.
Inhibition of regulated exocytosis by botulinum toxins type A and B was studied in chromaffin cells. Both virtually abolished catecholamine release triggered from intact cells by depolarising stimuli, whereas the blockade by type A, but not B, was only partial after cell permeabilisation and direct stimulation of exocytosis by Ca(2+). Botulinum toxin A did not alter the [Ca(2+)]-dependency of exocytosis in permeabilised cells but, rather, proportionally reduced the amount of release at each concentration tested. Likewise, this toxin decreased the extents of Ca(2+)-induced structural changes in SNAP-25, synaptobrevin and syntaxin (known collectively as SNAREs), whilst leaving their [Ca(2+)]-sensitivity unaltered. Thus, botulinum toxin A does not reduce the Ca(2+)-sensitivity of the exocytosis sensor, but hinders transmission of the signal to the SNAREs which mediate fusion.
Lawrence
Gary W
GW
Centre for Neurobiochemistry, Department of Biological Sciences, Imperial College of Science, Technology and Medicine, London, UK. g.lawrence@ic.ac.uk
Foran
Patrick
P
Oliver Dolly
J
J
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors*; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / 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
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D001905:Botulinum Toxins; D002118:Calcium