期刊
NEURON
卷 96, 期 6, 页码 1317-+出版社
CELL PRESS
DOI: 10.1016/j.neuron.2017.10.028
关键词
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资金
- National Key Research and Development Program of China [2016YFA0500400, 2016YFA0500401]
- National Natural Science Foundation of China [31228010, 31171026, 31100597, 31327901, 31221002, 31330024, 31670843, 31521062, 31400708, 21790390, 21790394]
- National Basic Research Program of China [2012CB518006]
- Key Research and Development Program of Shaanxi Province of China [2017SF-113]
- Fundamental Research Funds for the Central Universities of China [2017qngz10]
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.
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