Sakaba Takeshi, Stein Alexander, Jahn Reinhard, Neher Erwin
Department of Neurobiology and Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
Science. 2005 Jul 15;309(5733):491-4. doi: 10.1126/science.1112645.
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.
神经递质的释放由钙离子触发，并且严重依赖于三种可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白的正确功能。利用大鼠的大萼 Held 突触前终末，我们发现梭菌神经毒素对不同SNARE蛋白的切割会导致神经递质释放产生明显的动力学变化。当使用笼锁钙直接在突触前终末提高钙离子浓度时，肉毒杆菌毒素A（BoNT/A）对SNAP - 25的切割会使释放的钙敏感性大幅降低，而使用肉毒杆菌毒素C1（BoNT/C1）对 syntaxin 的切割以及使用破伤风毒素（TeNT）对突触小泡蛋白的切割会产生全或无的阻断，且不改变剩余囊泡的动力学。当通过通道的钙内流刺激释放时，BoNT/C1和TeNT之间出现了差异，这表明突触小泡蛋白的切割改变了通道与有释放能力囊泡之间的偶联。
