Influence of the NR3A subunit on NMDA receptor functions.
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.
Henson
Maile A
MA
Curriculum in Neurobiology, Neuroscience Center, Neurodevelopmental Disorders Research Center, Chapel Hill, NC 27599, USA.
Roberts
Adam C
AC
Pérez-Otaño
Isabel
I
Philpot
Benjamin D
BD
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D006801:Humans; D009422:Nervous System Diseases / Q000503:physiopathology; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018009:Receptors, Glycine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D018690:Excitatory Amino Acid Agonists; C464437:NR3A NMDA receptor; D021122:Protein Subunits; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate