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Gene Review

Grik2  -  glutamate receptor, ionotropic, kainate 2

Rattus norvegicus

Synonyms: GluK2, GluR-6, GluR6, Glur6, Glutamate receptor 6, ...
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Disease relevance of Grik2


Psychiatry related information on Grik2

  • 7. The effects of both calcineurin and PKA on Po,peak for GluR6 receptors in excised patches occur without any detectable changes to response time course, desensitization, or chord conductance [5].

High impact information on Grik2

  • Here we report that the GluR6 glutamate receptor, transiently expressed in mammalian cells, is directly phosphorylated by PKA, and that intracellularly applied PKA increases the amplitude of the glutamate response [6].
  • Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase [6].
  • The pharmacological profile was independent of AMPA receptors or the GluR5 subunit, indicating a possible role for the GluR6 subunit [7].
  • These data suggest how KARs, putatively containing GluR6, directly increase excitability of CA1 pyramidal cells and help explain the propensity for seizure activity following KAR activation [7].
  • In addition, we show that the Q/R site from the GluR6 subunit controls functional properties of native kainate receptors [8].

Chemical compound and disease context of Grik2


Biological context of Grik2


Anatomical context of Grik2


Associations of Grik2 with chemical compounds

  • We report the crystal structure of the glycosylated ligand-binding (S1S2) domain of the kainate receptor subunit GluR6, in complex with the agonist domoate [17].
  • Subtle differences in these contacts provide a structural explanation for why GluR2 L483Y and GluR3 L507Y are nondesensitizing, but GluR6, which has a tyrosine at that site, is not [17].
  • Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid [17].
  • The EC50 for receptor activation by 2S,4R-4MG (1.0 microM) was similar to that for kainic acid (1.8 microM), but 2S,4R-4MG was significantly more potent than kainate, glutamate or the other diastereomers of 4-methylglutamate at producing steady-state desensitization of GluR6 receptors [18].
  • The potencies of kainate, glutamate and diastereomers of 4-methylglutamate were determined for activation and steady-state desensitization of GluR6 and dorsal root ganglion-type kainate receptors using whole-cell voltage clamp [18].

Physical interactions of Grik2


Regulatory relationships of Grik2


Other interactions of Grik2

  • At a moderate level were GluR6, NR2B, and NR2D [22].
  • All four AMPA subunits and GluR6 and GluR7 mRNAs were expressed highly in the perinuclear PVN region and the subparaventricular zone [23].
  • Differently, Glur6 and KA2 mRNAs show a sharp increase at E14.5 and decrease thereafter, reaching the lowest levels during late embryonic and postnatal development [24].
  • In common with the AMPA receptor subunit GluR2, the GluR6 S1S2 domain associates as a dimer, with many of the interdimer contacts being conserved [17].
  • Low levels of GluR1, GluR4 and GluR6 expression were detected in various tissues of the cochlea during development [25].

Analytical, diagnostic and therapeutic context of Grik2


  1. Neuroprotective effects of GluR6 antisense oligodeoxynucleotides on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 region. Pei, D.S., Guan, Q.H., Sun, Y.F., Zhang, Q.X., Xu, T.L., Zhang, G.Y. J. Neurosci. Res. (2005) [Pubmed]
  2. RNA editing of glutamate receptor subunits GluR2, GluR5 and GluR6 in transient cerebral ischemia in the rat. Paschen, W., Schmitt, J., Uto, A. J. Cereb. Blood Flow Metab. (1996) [Pubmed]
  3. Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Brandstätter, J.H., Hartveit, E., Sassoè-Pognetto, M., Wässle, H. Eur. J. Neurosci. (1994) [Pubmed]
  4. Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: evidence for independent developmental, pathological and cellular regulation. Bernard, A., Ferhat, L., Dessi, F., Charton, G., Represa, A., Ben-Ari, Y., Khrestchatisky, M. Eur. J. Neurosci. (1999) [Pubmed]
  5. Control of rat GluR6 glutamate receptor open probability by protein kinase A and calcineurin. Traynelis, S.F., Wahl, P. J. Physiol. (Lond.) (1997) [Pubmed]
  6. Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase. Raymond, L.A., Blackstone, C.D., Huganir, R.L. Nature (1993) [Pubmed]
  7. Metabotropic-mediated kainate receptor regulation of IsAHP and excitability in pyramidal cells. Melyan, Z., Wheal, H.V., Lancaster, B. Neuron (2002) [Pubmed]
  8. Kainate receptor subunits expressed in single cultured hippocampal neurons: molecular and functional variants by RNA editing. Ruano, D., Lambolez, B., Rossier, J., Paternain, A.V., Lerma, J. Neuron (1995) [Pubmed]
  9. Altered interaction between PSD-95 and the NMDA receptor following transient global ischemia. Takagi, N., Logan, R., Teves, L., Wallace, M.C., Gurd, J.W. J. Neurochem. (2000) [Pubmed]
  10. Calcium/calmodulin-dependent protein kinase II (CaMKII), through NMDA receptors and L-Voltage-gated channels, modulates the serine phosphorylation of GluR6 during cerebral ischemia and early reperfusion period in rat hippocampus. Hao, Z.B., Pei, D.S., Guan, Q.H., Zhang, G.Y. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  11. The PDZ1 domain of SAP90. Characterization of structure and binding. Piserchio, A., Pellegrini, M., Mehta, S., Blackman, S.M., Garcia, E.P., Marshall, J., Mierke, D.F. J. Biol. Chem. (2002) [Pubmed]
  12. Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5, GluR6, and GluR7 mRNA and Protein Expression in rat hippocampus. Ullal, G., Fahnestock, M., Racine, R. Epilepsia (2005) [Pubmed]
  13. Functional kainate-selective glutamate receptors in cultured hippocampal neurons. Lerma, J., Paternain, A.V., Naranjo, J.R., Mellström, B. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  14. A complex mosaic of high-affinity kainate receptors in rat brain. Wisden, W., Seeburg, P.H. J. Neurosci. (1993) [Pubmed]
  15. Expression of GluR6/7 subunits of kainate receptors in rat adenohypophysis. Hinoi, E., Yoneda, Y. Neurochem. Int. (2001) [Pubmed]
  16. Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain. Wüllner, U., Standaert, D.G., Testa, C.M., Penney, J.B., Young, A.B. Brain Res. (1997) [Pubmed]
  17. Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid. Nanao, M.H., Green, T., Stern-Bach, Y., Heinemann, S.F., Choe, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  18. Desensitization of kainate receptors by kainate, glutamate and diastereomers of 4-methylglutamate. Jones, K.A., Wilding, T.J., Huettner, J.E., Costa, A.M. Neuropharmacology (1997) [Pubmed]
  19. Activation of c-Jun NH2-terminal kinase 3 is mediated by the GluR6.PSD-95.MLK3 signaling module following cerebral ischemia in rat hippocampus. Tian, H., Zhang, Q.G., Zhu, G.X., Pei, D.S., Guan, Q.H., Zhang, G.Y. Brain Res. (2005) [Pubmed]
  20. GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors. Paternain, A.V., Herrera, M.T., Nieto, M.A., Lerma, J. J. Neurosci. (2000) [Pubmed]
  21. Stable expression of a functional GluR6 homomeric glutamate receptor channel in mammalian cells. Tygesen, C.K., Rasmussen, J.S., Jones, S.V., Hansen, A., Hansen, K., Andersen, P.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  22. Expression of AMPA, kainate, and NMDA receptor subunits in cochlear and vestibular ganglia. Niedzielski, A.S., Wenthold, R.J. J. Neurosci. (1995) [Pubmed]
  23. Expression of ionotropic glutamate receptor subunit mRNAs in the hypothalamic paraventricular nucleus of the rat. Herman, J.P., Eyigor, O., Ziegler, D.R., Jennes, L. J. Comp. Neurol. (2000) [Pubmed]
  24. Ontogeny of kainate receptor gene expression in the developing rat midbrain and striatum. Lilliu, V., Perrone-Capano, C., Pernas-Alonso, R., Diaz Trelles, R., Luca Colucci d'Amato, G., Zuddas, A., di Porzio, U. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  25. Distribution of non-NMDA glutamate receptor mRNAs in the developing rat cochlea. Luo, L., Brumm, D., Ryan, A.F. J. Comp. Neurol. (1995) [Pubmed]
  26. Activation of spinal kainate receptors after inflammation: behavioral hyperalgesia and subunit gene expression. Guo, W., Zou, S., Tal, M., Ren, K. Eur. J. Pharmacol. (2002) [Pubmed]
  27. Glutamate receptor agonists stimulate diverse calcium responses in different types of cultured rat cortical glial cells. Holzwarth, J.A., Gibbons, S.J., Brorson, J.R., Philipson, L.H., Miller, R.J. J. Neurosci. (1994) [Pubmed]
  28. Role of kainate receptor activation and desensitization on the [Ca(2+)](i) changes in cultured rat hippocampal neurons. Silva, A.P., Malva, J.O., Ambrósio, A.F., Salgado, A.J., Carvalho, A.P., Carvalho, C.M. J. Neurosci. Res. (2001) [Pubmed]
  29. Larger intercellular variation in (Q/R) editing of GluR6 than GluR5 revealed by single cell RT-PCR. Christensen, K.V., Dai, W.M., Lambert, J.D., Egebjerg, J. Neuroreport (2000) [Pubmed]
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