Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation
Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation
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DOI：
10.1038/71090
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发表时间：
2000-01-01
影响因子：
25
通讯作者：
Lipton, SA
中科院分区：
文献类型：
--
作者：
Choi, YB;Tenneti, L;Lipton, SA
一些离子通道被认为是由一氧化氮(NO)直接调节的，但这种调节的分子基础尚不清楚。在此，我们发现NMDAR相关离子通道不仅受外源性NO的调节，也受内源性NO的调节。定点突变在NR2A亚单位上发现了一个关键的半胱氨酸残基(Cys399)，其生理条件下的S-亚硝化(NO+转移)是这种调控的基础。在表达NMDAR的细胞系统中，如果突变的NR2a亚基中的半胱氨酸被丙氨酸取代，内源性NO的作用就会消失。因此，内源性S亚硝化对离子通道活动具有调节作用。
Several ion channels are thought to be directly modulated by nitric-oxide (NO), but the molecular basis of this regulation is unclear. Here we show that the NMDA receptor (NMDAR)-associated ion channel was modulated not only by exogenous NO but also by endogenous NO. Site-directed mutagenesis identified a critical cysteine residue (Cys 399) on the NR2A subunit whose S-nitrosylation (NO+ transfer) under physiological conditions underlies this modulation. In cell systems expressing NMDARs with mutant NR2A subunits in which this single cysteine was replaced by an alanine, the effect of endogenous NO was lost. Thus endogenous S-nitrosylation can regulate ion channel activity.