CaV2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in Mammalian Sensory Neurons
CaV2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in Mammalian Sensory Neurons
复制标题
CaV2.2 控制哺乳动物感觉神经元中钙独立但电压依赖性的分泌
DOI：
10.1016/j.neuron.2017.10.028
复制
发表时间：
2017-12-20
期刊：
影响因子：
16.2
通讯作者：
Zhou, Zhuan
中科院分区：
文献类型：
--
作者：
Chai, Zuying;Wang, Changhe;Zhou, Zhuan
动作电位诱导膜去极化，并通过电压门控Ca 2+通道的Ca 2+内流触发细胞内游离Ca 2+浓度（Ca 2+）依赖性分泌（CDS）。我们报道了一种由动作电位本身触发的背根神经节神经元胞吐的新类型--钙非依赖性但电压依赖性分泌（CiVDS）。在这里，我们揭示了CiVDS的分子机制，包括电压传感器，融合机器和它们的连接器。具体而言，电压门控N型Ca 2+通道（Ca（V）2.2）是触发CiVDS的电压传感器，SNARE复合物起囊泡融合机器的作用，Ca（V）2.2的“同步印记”充当电压传感器和融合机器之间的接头，并且ATP是CiVDS囊泡的货物。因此，CiVDS从索马释放ATP，而CDS从突触前末梢释放谷氨酸，建立Ca（V）2.2-SNARE“电压门控融合孔”作为与经典“Ca 2+门控融合孔”途径共存的新途径，用于初级感觉神经元中动作电位后的神经递质释放。
Action potential induces membrane depolarization and triggers intracellular free Ca2+ concentration (Ca2+)-dependent secretion (CDS) via Ca2+ influx through voltage-gated Ca2+ channels. We report a new type of somatic exocytosis triggered by the action potential per se-Ca2+-independent but voltage-dependent secretion (CiVDS)-in dorsal root ganglion neurons. Here we uncovered the molecular mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their linker. Specifically, the voltage-gated N-type Ca2+ channel (Ca(V)2.2) is the voltage sensor triggering CiVDS, the SNARE complex functions as the vesicle fusion machinery, the "synprint'' of Ca(V)2.2 serves as a linker between the voltage sensor and the fusion machinery, and ATP is a cargo of CiVDS vesicles. Thus, CiVDS releases ATP from the soma while CDS releases glutamate from presynaptic terminals, establishing the Ca(V)2.2-SNARE "voltage-gating fusion pore'' as a novel pathway co-existing with the canonical "Ca2+-gating fusion pore'' pathway for neurotransmitter release following action potentials in primary sensory neurons.