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GRIN3A  -  glutamate receptor, ionotropic, N-methyl-D...

Homo sapiens

Synonyms: GluN3A, Glutamate receptor ionotropic, NMDA 3A, KIAA1973, N-methyl-D-aspartate receptor subtype 3A, NMDAR-L, ...
 
 
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Disease relevance of GRIN3A

 

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

 

Biological context of GRIN3A

 

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

References

  1. Characterization of a soluble ligand binding domain of the NMDA receptor regulatory subunit NR3A. Yao, Y., Mayer, M.L. J. Neurosci. (2006) [Pubmed]
  2. NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder. Mueller, H.T., Meador-Woodruff, J.H. Schizophr. Res. (2004) [Pubmed]
  3. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Das, S., Sasaki, Y.F., Rothe, T., Premkumar, L.S., Takasu, M., Crandall, J.E., Dikkes, P., Conner, D.A., Rayudu, P.V., Cheung, W., Chen, H.S., Lipton, S.A., Nakanishi, N. Nature (1998) [Pubmed]
  4. Genetic Variations of the NR3A Subunit of the NMDA Receptor Modulate Prefrontal Cerebral Activity in Humans. Gallinat, J., G??tz, T., Kalus, P., Bajbouj, M., Sander, T., Winterer, G. Journal of cognitive neuroscience (2007) [Pubmed]
  5. Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B. Andersson, O., Stenqvist, A., Attersand, A., von Euler, G. Genomics (2001) [Pubmed]
  6. An NMDA receptor signaling complex with protein phosphatase 2A. Chan, S.F., Sucher, N.J. J. Neurosci. (2001) [Pubmed]
  7. Molecular interaction of NMDA receptor subunit NR3A with protein phosphatase 2A. Ma, O.K., Sucher, N.J. Neuroreport (2004) [Pubmed]
  8. Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. Perez-Otano, I., Schulteis, C.T., Contractor, A., Lipton, S.A., Trimmer, J.S., Sucher, N.J., Heinemann, S.F. J. Neurosci. (2001) [Pubmed]
  9. NR3A modulates the outer vestibule of the "NMDA" receptor channel. Wada, A., Takahashi, H., Lipton, S.A., Chen, H.S. J. Neurosci. (2006) [Pubmed]
  10. Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain. Wong, H.K., Liu, X.B., Matos, M.F., Chan, S.F., Pérez-Otaño, I., Boysen, M., Cui, J., Nakanishi, N., Trimmer, J.S., Jones, E.G., Lipton, S.A., Sucher, N.J. J. Comp. Neurol. (2002) [Pubmed]
  11. Cloning and expression of the human N-methyl-D-aspartate receptor subunit NR3A. Eriksson, M., Nilsson, A., Froelich-Fabre, S., Akesson, E., Dunker, J., Seiger, A., Folkesson, R., Benedikz, E., Sundström, E. Neurosci. Lett. (2002) [Pubmed]
  12. Molecular modeling of the ligand-binding domains of the NR3A and NR3B subunits of the NMDA receptor. Belenikin, M.S., Costantino, G., Palyulin, V.A., Pellicciari, R., Zefirov, N.S. Dokl. Biochem. Biophys. (2003) [Pubmed]
  13. Characterization of the glutametergic system in MG-63 osteoblast-like osteosarcoma cells. Kalariti, N., Lembessis, P., Koutsilieris, M. Anticancer Res. (2004) [Pubmed]
 
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