S-亚硝基化修饰对NMDA受体偶联离子通道调节作用的分子基础

Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation.

作者信息

Choi Y B, Tenneti L, Le D A, Ortiz J, Bai G, Chen H S, Lipton S A

机构信息

Cerebrovascular and Neuroscience Research Institute, Brigham and Women's Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Nat Neurosci. 2000 Jan;3(1):15-21. doi: 10.1038/71090.

DOI:10.1038/71090

PMID:10607390

Abstract

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.

摘要

几种离子通道被认为可直接由一氧化氮（NO）调节，但这种调节的分子基础尚不清楚。在此我们表明，N-甲基-D-天冬氨酸受体（NMDAR）相关离子通道不仅受外源性NO调节，也受内源性NO调节。定点诱变确定了NR2A亚基上一个关键的半胱氨酸残基（Cys 399），其在生理条件下的S-亚硝基化（NO+转移）是这种调节的基础。在表达带有突变NR2A亚基（其中该单个半胱氨酸被丙氨酸取代）的NMDAR的细胞系统中，内源性NO的作用消失。因此，内源性S-亚硝基化可调节离子通道活性。