Disease relevance of GRIN3A

• Here, a soluble NR3A ligand binding domain (NR3A S1S2) was constructed based on amino acid sequence alignments with other glutamate receptor ion channels and is expressed in Escherichia coli [1].

Psychiatry related information on GRIN3A

• NR3A mRNA was significantly decreased by 12% in bipolar disorder relative to the comparison group in DLPFC, although there were no gyral versus sulcal differences [2].

High impact information on GRIN3A

• Genetic knockout of NR3A in mice results in enhanced NMDA responses and increased dendritic spines in early postnatal cerebrocortical neurons [3].
• In single-channel recordings from Xenopus oocytes, addition of NR3A to NR1 and NR2 leads to the appearance of a smaller unitary conductance [3].
• Introduction: Recently, a novel N-methyl-D-aspartate (NMDA) receptor subunit, NR3A, has been discovered in the brain [4].
• Because the NR3A is expressed in the human prefrontal cortex, we hypothesized that genetic variations of the NR3A subunit modulate prefrontal activation [4].
• The results underline the pivotal role of glutamate in frontal lobe function and indicate that the NR3A subunit could be a plausible candidate gene for diseases with prefrontal dysfunctions [4].

Chemical compound and disease context of GRIN3A

• NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder [2].

Biological context of GRIN3A

• GRIN3A localizes to chromosome 9q34, in the region 13-34, and consists of nine coding exons [5].
• The catalytic subunit of the serine-threonine PP2A was found to be associated with the NR3A carboxyl domain [6].
• A cDNA library was screened by the yeast two-hybrid method using the NR3A carboxyl domain as the bait [6].
• We performed alanine-scanning mutagenesis in the PP2A-binding domain of the NR3A C-terminal (NR3Ac), then co-expressed the mutants together with the PP2A catalytic subunit in a yeast two-hybrid system and human embryonic kidney (HEK) 293 cells [7].

Anatomical context of GRIN3A

• Coexpression of NR1-1a facilitates the surface expression of NR3A-containing receptors, reduces the accumulation of NR3A subunits in the endoplasmic reticulum, and induces the appearance of intracellular clusters where both subunits are colocalized [8].
• NR3A modulates the outer vestibule of the "NMDA" receptor channel [9].
• NR3A protein was also expressed in the cerebellar cortex, whereas only weak signal was detected in the previous in situ studies by using riboprobes [10].
• At an ultrastructural level, NR3A was associated specifically with asymmetrical synapses and localized to postsynaptic membranes [10].
• NR3A protein was found to peak at postnatal day (P) 8, and to decrease gradually from P12 to adulthood in the rat central nervous system [10].

Associations of GRIN3A with chemical compounds

• Cloning and expression of the human N-methyl-D-aspartate receptor subunit NR3A [11].
• Proteolysis protection experiments reveal that CNQX and CGP78608 bind to and stabilize domain 1 of NR3A S1S2 but increase proteolysis of domain 2, indicating that they produce conformational changes distinct from those induced by glycine and D-serine [1].
• Using the Xenopus oocyte expression system and the SCAM (substituted cysteine accessibility method), we found that M3 segments of both NR1 and NR3A form a narrow constriction in the outer vestibule of the channel, which prevents passage of externally applied sulfhydryl-specific agents [9].
• We found that mutation of leucine 958, leucine 973 or histidine 974 or deletion of a spacer sequence of more than six amino acids between leucine 958 and histidine 974 disrupted the NR3A/PP2A interaction [7].
• Additionally, in the M2 segment, our data suggest that the amino acid at the asparagine (N) site of NR1, but not NR3A, contributes to the selectivity filter of NR1/3A channels [9].

Other interactions of GRIN3A

• The NR3A subunit, which in rodents is predominantly expressed during early development, seems to function by reducing the NMDA receptor response [11].
• Molecular modeling of the ligand-binding domains of the NR3A and NR3B subunits of the NMDA receptor [12].
• In addition, we documented, for the first time, the mRNA expression of the NR3A, EAAT1, mGlu.R1, mGlu.R2, mGlu.R3, mGluR.4, mGlu.R5 and mGlu.R8 mRNA [13].

Analytical, diagnostic and therapeutic context of GRIN3A

• Immunoprecipitation studies indicated that the NR3A subunit formed a stable complex with PP2A in the rat brain in vivo [6].
• We therefore conclude that NR3A modulates the NR1/NR3A permeation pathway via a novel mechanism of forming a narrow constriction at the outer channel vestibule [9].
• After purification by affinity, gel filtration, and ion exchange chromatography, NR3A S1S2 behaves as a monomer even at a concentration of 20 mg/ml, as determined by size-exclusion chromatography and dynamic light scattering [1].

References