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Science 309 (5733): 491-494

Copyright © 2005 by the American Association for the Advancement of Science

Distinct Kinetic Changes in Neurotransmitter Release After SNARE Protein Cleavage

Takeshi Sakaba,* Alexander Stein, Reinhard Jahn, Erwin Neher*

Abstract: 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.

Department of Neurobiology and Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.

* To whom correspondence should be addressed. E-mail: eneher{at}gwdg.de (E.N.); tsakaba{at}gwdg.de (T.S.)

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