Department of Neuroscience, Faculty of Health and Medical Sciences, 2200 Copenhagen N, University of Copenhagen, Copenhagen, Denmark.
Heidelberg University Biochemistry Center, 69120 Heidelberg, Germany.
Cell Rep. 2019 Feb 26;26(9):2340-2352.e5. doi: 10.1016/j.celrep.2019.01.103.
Information transfer across CNS synapses depends on the very low basal vesicle fusion rate and the ability to rapidly upregulate that rate upon Ca influx. We show that local electrostatic repulsion participates in creating an energy barrier, which limits spontaneous synaptic transmission. The barrier amplitude is increased by negative charges and decreased by positive charges on the SNARE-complex surface. Strikingly, the effect of charges on the barrier is additive and this extends to evoked transmission, but with a shallower charge dependence. Action potential-driven synaptic release is equivalent to the abrupt addition of ∼35 positive charges to the fusion machine. Within an electrostatic model for triggering, the Ca sensor synaptotagmin-1 contributes ∼18 charges by binding Ca, while also modulating the fusion barrier at rest. Thus, the energy barrier for synaptic vesicle fusion has a large electrostatic component, allowing synaptotagmin-1 to act as an electrostatic switch and modulator to trigger vesicle fusion.
信息在中枢神经系统突触间的传递依赖于极低的基础囊泡融合率和钙内流时快速上调该速率的能力。我们发现局部静电斥力参与形成了一个能量障碍，限制了自发的突触传递。在 SNARE 复合物表面带负电荷会增加障碍幅度，带正电荷则会降低障碍幅度。引人注目的是，电荷对障碍的影响是累加的，这也适用于诱发的传递，但电荷依赖性较浅。动作电位驱动的突触释放相当于向融合机器中突然添加约 35 个正电荷。在触发的静电模型中，结合钙离子的突触融合蛋白 synaptotagmin-1 通过结合 Ca 贡献约 18 个电荷，同时在静止时调节融合障碍。因此，突触囊泡融合的能量障碍具有很大的静电分量，允许突触融合蛋白 synaptotagmin-1 作为静电开关和调节剂来触发囊泡融合。
