Nature Neuroscience
3, 15 - 21 (2000)
doi:10.1038/71090
Molecular basis of NMDA receptor-coupled ion channel modulation by
S-nitrosylationYun-Beom Choi1, Lalitha Tenneti1, Dean A. Le1, Justin Ortiz1, Guang Bai1, Huei-Sheng Vincent Chen1
& Stuart A. Lipton1, 21
Cerebrovascular and Neuroscience Research Institute,
Brigham and Women's Hospital, and Program in Neuroscience, Harvard Medical
School, 221 Longwood Avenue, LMRC First Floor,
Boston, Massachusetts 02115, USA
2
Present address: Del E. Webb Center for Neuroscience
and Aging Research, The Burnham Institute, 10901 North Torrey
Pines Road, La Jolla, California 92037,
USA
Correspondence should be addressed to Stuart A. Lipton slipton@burnham-inst.orgSeveral 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.
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