Influence of the NR3A subunit on NMDA receptor functions |
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| Authors: | Maile A. Henson,Adam C. Roberts,Isabel Pé rez-Otañ o,Benjamin D. Philpot |
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| Affiliation: | 1. Curriculum in Neurobiology, Neuroscience Center, Neurodevelopmental Disorders Research Center, and Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC 27599, USA;2. Cellular Neurobiology Laboratory, Departamento de Neurociencias, Centro de Investigación Médica Aplicada (CIMA) y Universidad de Navarra, 31008 Pamplona, Spain |
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| Abstract: | ![]()
Various combinations of subunits assemble to form the NMDA-type glutamate receptor (NMDAR), generating diversity in its functions. Here we review roles of the unique NMDAR subunit, NR3A, which acts in a dominant-negative manner to suppress receptor activity. NR3A-containing NMDARs display striking regional and temporal expression specificity, and, unlike most other NMDAR subtypes, they have a low conductance, are only modestly permeable to Ca2+, and pass current at hyperpolarized potentials in the presence of magnesium. While glutamate activates triheteromeric NMDARs composed of NR1/NR2/NR3A subunits, glycine is sufficient to activate diheteromeric NR1/NR3A-containing receptors. NR3A dysfunction may contribute to neurological disorders involving NMDARs, and the subunit offers an attractive therapeutic target given its distinct pharmacological and structural properties. |
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| Keywords: | NMDAR, N-methyl-d-aspartate receptor AMPAR, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor PKA, protein kinase A PKC, protein kinase C PTK, protein tyrosine kinase CaMKII, calcium/calmodulin-dependent kinase II TM, transmembrane region P, postnatal day PSD, postsynaptic density ER, endoplasmic reticulum PP2A, protein phosphatase 2A LTP, long-term potentiation LTD, long-term depression mEPSC, miniature excitatory postsynaptic current DLPFC, dorsolateral prefrontal cortex SP, signal peptide glyc, glycosylation S1&ndash S2, extracellular ligand-binding domain/glycine binding pocket of NMDARs mo, months yr, year EC, entorhinal cortex VC, visual cortex FC, frontal cortex Hpc, hippocampus Str/GP, striatum/globus pallidus Olf. Bulb, olfactory bulb pre, presynaptic bouton post, postsynaptic spine Mg2+, magnesium Glu, glutamate Gly, glycine Ca2+, calcium pA, picoamps ms, milliseconds |
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