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 Ca(2+), 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.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / anatomy & histology
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Brain / embryology
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Brain / growth & development
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Brain / metabolism
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Excitatory Amino Acid Agonists / metabolism
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Humans
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Nervous System Diseases / physiopathology
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Protein Structure, Tertiary
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Protein Subunits / chemistry
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Protein Subunits / genetics
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Protein Subunits / metabolism*
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Receptors, Glutamate / chemistry
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Receptors, Glutamate / genetics
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Receptors, Glutamate / metabolism
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Receptors, Glycine / chemistry
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Receptors, Glycine / genetics
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Receptors, Glycine / metabolism
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Receptors, N-Methyl-D-Aspartate / chemistry
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Tissue Distribution
Substances
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Excitatory Amino Acid Agonists
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NR3A NMDA receptor
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Protein Subunits
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Receptors, Glutamate
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Receptors, Glycine
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Receptors, N-Methyl-D-Aspartate