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Gene Review

Gria2  -  glutamate receptor, ionotropic, AMPA2...

Mus musculus

Synonyms: AMPA-selective glutamate receptor 2, GluA2, GluR-2, GluR-B, GluR-K2, ...
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Disease relevance of Gria2


Psychiatry related information on Gria2

  • At 2 months after pretreatment, we measured levels of AMPA GluR2/3 subunits, thought to be involved in the control of addictive behaviors [6].

High impact information on Gria2

  • A functionally critical position (Q/R site) of the AMPA receptor subunit GluR-B is controlled by RNA editing that operates in the nucleus, since in brain and clonal cell lines of neural origin, unspliced GluR-B transcripts occur edited in the Q/R site CAG codon and, additionally, in intronic adenosines [7].
  • Transfection of GluR-B gene constructs into PC12 cells revealed that the proximal part of the intron downstream of the unedited exonic site is required for Q/R site editing [7].
  • Base conversion in the channel-coding region of GluR-B directed by base paired sequences may be executed by a ubiquitous nuclear adenosine deaminase specific for double-stranded RNA [7].
  • The critical position specifies an ion channel determinant, the Q/R site, in AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor GluR-B pre-messenger RNA [8].
  • These effects of deltaFosB appear to be mediated partly by induction of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole) glutamate receptor subunit GluR2 in the nucleus accumbens [9].

Chemical compound and disease context of Gria2


Biological context of Gria2

  • We show here that the double knockout mice are severely impaired in basal synaptic transmission, demonstrating that GluR2/3 are essential to maintain adequate synaptic transmission in vivo [11].
  • Here, we demonstrate that NO-evoked postsynaptic LTP in mice cerebellum was blocked by botulinum toxin and enhanced by prior treatment with phorbol ester, which is known to induce GluR2 endocytosis [12].
  • These data indicate that tyrosine phosphorylation of tyrosine 876 on the GluR2 C terminus by Src family tyrosine kinases is important for the regulation of AMPA receptor function and may be important for synaptic plasticity [13].
  • Thus, changes in GluR-B gene expression and Q/R site editing can affect critical architectural and functional aspects of excitatory principal neurons [14].
  • The seizure-prone phenotype correlated with an increase in the macroscopic conductance, as independently revealed by the effect of a transgene for a Q/R-site-altered GluR-B subunit [14].

Anatomical context of Gria2


Associations of Gria2 with chemical compounds

  • Synaptic transmission and plasticity in the absence of AMPA glutamate receptor GluR2 and GluR3 [11].
  • Thus, AMPAR recycling elicited by NMDA neurotransmission is mediated by a cascade involving NMDA activation of neuronal NO synthase to form NO, leading to S-nitrosylation of NSF which is thereby activated, enabling it to bind to GluR2 and promote the receptor's surface expression [18].
  • In cortical neuronal cultures AMPAR-mediated neurotoxicity paralleled the magnitude of kainate-evoked AMPAR-mediated currents, which were increased in neurons lacking GluR2 [19].
  • Ca(2+) permeability, although elevated in GluR2-deficient neurons, did not correlate with excitotoxicity [19].
  • Calcium permeability of L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in excitatory neurons of the mammalian brain is prevented by coassembly of the GluR-B subunit, which carries an arginine (R) residue at a critical site of the channel pore [20].

Physical interactions of Gria2

  • S-nitrosylation of NSF augments its binding to the AMPAR GluR2 subunit [18].

Regulatory relationships of Gria2

  • Cerebellar grafts transplanted into the pcd cerebellum expressed only GluRB and GluRC mRNAs, suggesting that donor cells express the appropriate subunits normally expressed by Purkinje neurons [21].

Other interactions of Gria2

  • The AMPA glutamate receptor (AMPAR) subunits GluR2 and GluR3 are thought to be important for synaptic targeting/stabilization of AMPARs and the expression of hippocampal long-term depression (LTD) [11].
  • Immunopurified full-length, native stargazin was shown to co-associate not only with GluR2 in vivo but also with full-length, native LC2 [22].
  • However, gray matter neurons did express GluR1 and GluR2, as well as GluR2/3 [17].
  • In dissociated hippocampal neuronal cultures, TNF-alpha exposure (6 nM, 15 min) induced a rapid increase in cell surface levels not only of GluR1, but also of the AMPAR subunit GluR2, on most neurons, without evident new protein synthesis [23].
  • Colocalisation experiments evidenced the expression of GluR1 and NR2A receptors in activated astrocytes from the cervical spinal cord of wobbler mice, GluR2 did not colocalise with GFAP positive cells [24].

Analytical, diagnostic and therapeutic context of Gria2


  1. Distribution of alpha-amino-3-hydroxy-5-methyl-4 isoazolepropionic acid and N-methyl-D-aspartate receptor subunits in the vestibular and spiral ganglia of the mouse during early development. Puyal, J., Sage, C., Demêmes, D., Dechesne, C.J. Brain Res. Dev. Brain Res. (2002) [Pubmed]
  2. The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain. Hartmann, B., Ahmadi, S., Heppenstall, P.A., Lewin, G.R., Schott, C., Borchardt, T., Seeburg, P.H., Zeilhofer, H.U., Sprengel, R., Kuner, R. Neuron (2004) [Pubmed]
  3. GluR2 deficiency accelerates motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis. Van Damme, P., Braeken, D., Callewaert, G., Robberecht, W., Van Den Bosch, L. J. Neuropathol. Exp. Neurol. (2005) [Pubmed]
  4. Role of GluR2 expression in AMPA-induced toxicity in cultured murine cerebral cortical neurons. Jensen, J.B., Lund, T.M., Timmermann, D.B., Schousboe, A., Pickering, D.S. J. Neurosci. Res. (2001) [Pubmed]
  5. Glutamate receptor 1-immunopositive neurons in the gliotic CA1 area of the mouse hippocampus after pilocarpine-induced status epilepticus. Tang, F.R., Chia, S.C., Zhang, S., Chen, P.M., Gao, H., Liu, C.P., Khanna, S., Lee, W.L. Eur. J. Neurosci. (2005) [Pubmed]
  6. Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine. Adriani, W., Granstrem, O., Macri, S., Izykenova, G., Dambinova, S., Laviola, G. Neuropsychopharmacology (2004) [Pubmed]
  7. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Higuchi, M., Single, F.N., Köhler, M., Sommer, B., Sprengel, R., Seeburg, P.H. Cell (1993) [Pubmed]
  8. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Higuchi, M., Maas, S., Single, F.N., Hartner, J., Rozov, A., Burnashev, N., Feldmeyer, D., Sprengel, R., Seeburg, P.H. Nature (2000) [Pubmed]
  9. Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Kelz, M.B., Chen, J., Carlezon, W.A., Whisler, K., Gilden, L., Beckmann, A.M., Steffen, C., Zhang, Y.J., Marotti, L., Self, D.W., Tkatch, T., Baranauskas, G., Surmeier, D.J., Neve, R.L., Duman, R.S., Picciotto, M.R., Nestler, E.J. Nature (1999) [Pubmed]
  10. Gamma-hydroxybutyric acid-induced absence seizures in GluR2 null mutant mice. Hu, R.Q., Cortez, M.A., Man, H.Y., Roder, J., Jia, Z., Wang, Y.T., Snead, O.C. Brain Res. (2001) [Pubmed]
  11. Synaptic transmission and plasticity in the absence of AMPA glutamate receptor GluR2 and GluR3. Meng, Y., Zhang, Y., Jia, Z. Neuron (2003) [Pubmed]
  12. A mechanism underlying AMPA receptor trafficking during cerebellar long-term potentiation. Kakegawa, W., Yuzaki, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Tyrosine phosphorylation and regulation of the AMPA receptor by SRC family tyrosine kinases. Hayashi, T., Huganir, R.L. J. Neurosci. (2004) [Pubmed]
  14. Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Feldmeyer, D., Kask, K., Brusa, R., Kornau, H.C., Kolhekar, R., Rozov, A., Burnashev, N., Jensen, V., Hvalby, O., Sprengel, R., Seeburg, P.H. Nat. Neurosci. (1999) [Pubmed]
  15. The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. Implications for glial-neuronal signaling. Stegmüller, J., Werner, H., Nave, K.A., Trotter, J. J. Biol. Chem. (2003) [Pubmed]
  16. Expression of 15 glutamate receptor subunits and various splice variants in tissue slices and single neurons of brainstem nuclei and potential functional implications. Paarmann, I., Frermann, D., Keller, B.U., Hollmann, M. J. Neurochem. (2000) [Pubmed]
  17. AMPA/kainate receptors in mouse spinal cord cell-specific display of receptor subunits by oligodendrocytes and astrocytes and at the nodes of Ranvier. Brand-Schieber, E., Werner, P. Glia (2003) [Pubmed]
  18. S-nitrosylation of N-ethylmaleimide sensitive factor mediates surface expression of AMPA receptors. Huang, Y., Man, H.Y., Sekine-Aizawa, Y., Han, Y., Juluri, K., Luo, H., Cheah, J., Lowenstein, C., Huganir, R.L., Snyder, S.H. Neuron (2005) [Pubmed]
  19. The influence of glutamate receptor 2 expression on excitotoxicity in Glur2 null mutant mice. Iihara, K., Joo, D.T., Henderson, J., Sattler, R., Taverna, F.A., Lourensen, S., Orser, B.A., Roder, J.C., Tymianski, M. J. Neurosci. (2001) [Pubmed]
  20. The AMPA receptor subunit GluR-B in its Q/R site-unedited form is not essential for brain development and function. Kask, K., Zamanillo, D., Rozov, A., Burnashev, N., Sprengel, R., Seeburg, P.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  21. AMPA receptor subunit RNA transcripts and [(3)H]AMPA binding in the cerebellum of normal and pcd mutant mice: an in situ hybridization study combined with receptor autoradiography. Fragioudaki, K., Giompres, P., Smith, A.L., Triarhou, L.C., Kouvelas, E.D., Mitsacos, A. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  22. Microtubule-associated protein light chain 2 is a stargazin-AMPA receptor complex-interacting protein in vivo. Ives, J.H., Fung, S., Tiwari, P., Payne, H.L., Thompson, C.L. J. Biol. Chem. (2004) [Pubmed]
  23. Tumor necrosis-factor-alpha (TNF-alpha) induces rapid insertion of Ca2+-permeable alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons. Ogoshi, F., Yin, H.Z., Kuppumbatti, Y., Song, B., Amindari, S., Weiss, J.H. Exp. Neurol. (2005) [Pubmed]
  24. Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice. Bigini, P., Gardoni, F., Barbera, S., Cagnotto, A., Fumagalli, E., Longhi, A., Corsi, M.M., Di Luca, M., Mennini, T. BMC neuroscience (2006) [Pubmed]
  25. Changes in AMPA subunit expression in the mouse brain after chronic treatment with the antidepressant maprotiline: a link between noradrenergic and glutamatergic function? Tan, C.H., He, X., Yang, J., Ong, W.Y. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2006) [Pubmed]
  26. Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Brusa, R., Zimmermann, F., Koh, D.S., Feldmeyer, D., Gass, P., Seeburg, P.H., Sprengel, R. Science (1995) [Pubmed]
  27. N-ethylmaleimide-sensitive factor is required for the synaptic incorporation and removal of AMPA receptors during cerebellar long-term depression. Steinberg, J.P., Huganir, R.L., Linden, D.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  28. RNA editing (Q/R site) and flop/flip splicing of AMPA receptor transcripts in young and old brains. Carlson, N.G., Howard, J., Gahring, L.C., Rogers, S.W. Neurobiol. Aging (2000) [Pubmed]
  29. Dendritic localization of Ca(2+)-permeable AMPA/kainate channels in hippocampal pyramidal neurons. Yin, H.Z., Sensi, S.L., Carriedo, S.G., Weiss, J.H. J. Comp. Neurol. (1999) [Pubmed]
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