Distinct kinetic changes in neurotransmitter release after SNARE protein cleavage.
Neurotransmitter release is triggered by calcium ions and depends critically on the correct function of three types of SNARE [soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor] proteins. With use of the large calyx of Held presynaptic terminal from rats, we found that cleavage of different SNARE proteins by clostridial neurotoxins caused distinct kinetic changes in neurotransmitter release. When elevating calcium ion concentration directly at the presynaptic terminal with the use of caged calcium, cleavage of SNAP-25 by botulinum toxin A (BoNT/A) produced a strong reduction in the calcium sensitivity for release, whereas cleavage of syntaxin using BoNT/C1 and synaptobrevin using tetanus toxin (TeNT) produced an all-or-nothing block without changing the kinetics of remaining vesicles. When stimulating release by calcium influx through channels, a difference between BoNT/C1 and TeNT emerged, which suggests that cleavage of synaptobrevin modifies the coupling between channels and release-competent vesicles.
Sakaba
Takeshi
T
Department of Neurobiology and Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany. tsakaba@gwdg.de
Stein
Alexander
A
Jahn
Reinhard
R
Neher
Erwin
E
D000200:Action Potentials; D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D013744:Tetanus Toxin / Q000378:metabolism / Q000494:pharmacology
D015220:Calcium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D013744:Tetanus Toxin; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; C096324:botulinum toxin type C; D002118:Calcium