Editors' ChoiceNeuroscience

Three Toxins Are Better Than One

Science's STKE  19 Jul 2005:
Vol. 2005, Issue 293, pp. tw267
DOI: 10.1126/stke.2932005tw267

Understanding molecular mechanisms of neurotransmitter release and short-term synaptic plasticity is one of the central questions in neuroscience. Sakaba et al. studied the roles of SNARE proteins in neurotransmitter release using clostridial neurotoxins. A detailed kinetic analysis of the action of several toxins revealed that the kinetics of transmitter release differs, depending on which SNARE proteins were cleaved. Toxins cleaving synaptobrevin and syntaxin reduced the number of fusion-competent vesicles without changing the Ca2+ sensitivity of the release apparatus of remaining vesicles. In contrast, toxins cleaving the C terminal of SNAP-25 reduced intracellular Ca2+ sensitivity of vesicle fusion, which suggests that the C terminal is important for driving rapid fusion. Furthermore, toxins cleaving synaptobrevin lead to a modification of the coupling between Ca2+ channels and release-competent vesicles.

T. Sakaba, A. Stein, R. Jahn, E. Neher, Distinct kinetic changes in neurotransmitter release after SNARE protein cleavage. Science 309, 491-494 (2005). [Abstract] [Full Text]