Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits

Jon E. Chatterton, Marc Awobuluyi, Louis S. Premkumar, Hiroto Takahashi, Maria Talantova, Yeonsook Shin, Jiankun Cui, Shichun Tu, Kevin A. Sevarino, Nobuki Nakanishi, Gang Tong, Stuart A. Lipton () and Dongxian Zhang ()
Additional contact information
Jon E. Chatterton: The Burnham Institute
Marc Awobuluyi: The Burnham Institute
Louis S. Premkumar: Southern Illinois University School of Medicine
Hiroto Takahashi: The Burnham Institute
Maria Talantova: The Burnham Institute
Yeonsook Shin: The Burnham Institute
Jiankun Cui: The Burnham Institute
Shichun Tu: The Burnham Institute
Kevin A. Sevarino: University of Connecticut Health Center
Nobuki Nakanishi: The Burnham Institute
Gang Tong: The Burnham Institute
Stuart A. Lipton: The Burnham Institute
Dongxian Zhang: The Burnham Institute

Nature, 2002, vol. 415, issue 6873, 793-798

Abstract: Abstract The N-methyl-d-aspartate subtype of glutamate receptor (NMDAR) serves critical functions in physiological and pathological processes in the central nervous system, including neuronal development, plasticity and neurodegeneration1,2. Conventional heteromeric NMDARs composed of NR1 and NR2A–D subunits3,4 require dual agonists, glutamate and glycine, for activation. They are also highly permeable to Ca2+, and exhibit voltage-dependent inhibition by Mg2+. Coexpression of NR3A with NR1 and NR2 subunits modulates NMDAR activity5,6,7. Here we report the cloning and characterization of the final member of the NMDAR family, NR3B, which shares high sequence homology with NR3A. From in situ and immunocytochemical analyses, NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely distributed5,6. Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co-assembles with NR1 to form excitatory glycine receptors that are unaffected by glutamate or NMDA, and inhibited by d-serine, a co-activator of conventional NMDARs. Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists. In cerebrocortical neurons containing NR3 family members, glycine triggers a burst of firing, and membrane patches manifest glycine-responsive single channels that are suppressible by d-serine. By itself, glycine is normally thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B ‘NMDARs’ constitute a type of excitatory glycine receptor.

Date: 2002
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DOI: 10.1038/nature715

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