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Grid2  -  glutamate receptor, ionotropic, delta 2

Mus musculus

Synonyms: B230104L07Rik, GluD2, GluR delta-2 subunit, GluRdelta2, Glutamate receptor ionotropic, delta-2, ...
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Disease relevance of Grid2

  • Results indicate that c-met (but not tpr-met) activation in B16 melanoma cells may increase their liver colonizing potential, probably by enhancing motility and invasion in response to paracrine interactions with its ligand [1].
  • Further characterization of GluR delta 2 signaling and the activation of apoptotic death in Lc Purkinje cells have begun to yield mechanistic insights into this neurodegenerative disease, and to highlight its relationship to neuronal loss following ischemia [2].
  • Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors [3].

Psychiatry related information on Grid2

  • Lurcher mutant mice (+/Lc) which exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nuclei were subjected to an active avoidance learning task; the animals' avoidance response must occur within a small time window after a short or a long delay [4].

High impact information on Grid2

  • Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR delta 2 mutant mice [5].
  • Analyses of the GluR delta 2 mutant mice reveal that the delta 2 subunit plays important roles in motor coordination, formation of parallel fiber-Purkinje cell synapses and climbing fiber-Purkinje cell synapses, and long-term depression of parallel fiber-Purkinje cell synaptic transmission [5].
  • To address these issues, we developed an antibody specific for the putative ligand-binding region of GluRdelta2, and application of this antibody to cultured Purkinje cells induced AMPA receptor endocytosis, attenuated synaptic transmission and abrogated long-term depression [6].
  • We have analyzed the phenotype of Lurcher/hotfoot heteroallelic mutants bearing only one copy of the Lurcher allele and no wild-type Grid2 [7].
  • Here we have identified protein interactions between GluRdelta2, a novel isoform of a PDZ domain-containing protein (nPIST) that binds to this receptor, and Beclin1. nPIST and Beclin1 can synergize to induce autophagy [8].

Biological context of Grid2

  • The mouse Grid2 gene consists of 16 exons, spanning approximately 1.4 Mb [9].
  • The Grid2 gene, which is mutated in lurcher (Lc) mice, maps to mouse chromosome 6 [10].
  • The increase in COX activity is likely to reflect an increase in oxidative phosphorylation to accommodate the energy demands of removing excess Na+ and Ca2+ entering the Purkinje cells in response to the Grid2 leak current [11].
  • Biotinylation assays indicated that GluR delta 2 lacking the C-terminal juxtamembrane region of 13 amino acids (region A) was not present on the cell surface [12].
  • A point mutation of the GluRdelta2 (A654T) glutamate receptor subunit converts it into a functional channel, and a spontaneous mutation at this site is thought to be responsible for the neurodegeneration of neurons in the Lurcher mouse [13].

Anatomical context of Grid2


Associations of Grid2 with chemical compounds


Physical interactions of Grid2


Co-localisations of Grid2


Regulatory relationships of Grid2


Other interactions of Grid2

  • We identified a novel GluRdelta2-interacting protein, named Delphilin, that contains a single PDZ domain and formin homology (FH) domains FH1 and FH2 plus coiled-coil structure [16].
  • Recently, ataxia in the hotfoot mouse ho4J was demonstrated to be caused by a deletion in the delta2 receptor gene (Grid2) removing the N-terminal 170 amino acids of the delta2 receptor [9].
  • Furthermore, GluRdelta2 and PSD-93 proteins were concentrated at the contacted portion of mismatched synapses, whereas AMPA receptors were distributed in both the contacted and dissociated portions [26].
  • Shank1 and Shank2 proteins as well as GluRdelta2 proteins were localized in the dendritic spines of cultured Purkinje cells [23].
  • Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development [19].

Analytical, diagnostic and therapeutic context of Grid2


  1. C-met activation is necessary but not sufficient for liver colonization by B16 murine melanoma cells. Lin, S., Rusciano, D., Lorenzoni, P., Hartmann, G., Birchmeier, W., Giordano, S., Comoglio, P., Burger, M.M. Clin. Exp. Metastasis (1998) [Pubmed]
  2. GluR delta 2 and the development and death of cerebellar Purkinje neurons in lurcher mice. Heintz, N., De Jager, P.L. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  3. Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. Liang, T.J., Reid, A.E., Xavier, R., Cardiff, R.D., Wang, T.C. J. Clin. Invest. (1996) [Pubmed]
  4. Timed active avoidance learning in lurcher mutant mice. Monfort, V., Chapillon, P., Mellier, D., Lalonde, R., Caston, J. Behav. Brain Res. (1998) [Pubmed]
  5. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR delta 2 mutant mice. Kashiwabuchi, N., Ikeda, K., Araki, K., Hirano, T., Shibuki, K., Takayama, C., Inoue, Y., Kutsuwada, T., Yagi, T., Kang, Y. Cell (1995) [Pubmed]
  6. New role of delta2-glutamate receptors in AMPA receptor trafficking and cerebellar function. Hirai, H., Launey, T., Mikawa, S., Torashima, T., Yanagihara, D., Kasaura, T., Miyamoto, A., Yuzaki, M. Nat. Neurosci. (2003) [Pubmed]
  7. Lurcher GRID2-induced death and depolarization can be dissociated in cerebellar Purkinje cells. Selimi, F., Lohof, A.M., Heitz, S., Lalouette, A., Jarvis, C.I., Bailly, Y., Mariani, J. Neuron (2003) [Pubmed]
  8. A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice. Yue, Z., Horton, A., Bravin, M., DeJager, P.L., Selimi, F., Heintz, N. Neuron (2002) [Pubmed]
  9. A hot spot for hotfoot mutations in the gene encoding the delta2 glutamate receptor. Wang, Y., Matsuda, S., Drews, V., Torashima, T., Meisler, M.H., Yuzaki, M. Eur. J. Neurosci. (2003) [Pubmed]
  10. The human glutamate receptor delta 2 gene (GRID2) maps to chromosome 4q22. Hu, W., Zuo, J., De Jager, P.L., Heintz, N. Genomics (1998) [Pubmed]
  11. Cytochrome oxidase activity is increased in +/Lc Purkinje cells destined to die. Vogel, M.W., Fan, H., Sydnor, J., Guidetti, P. Neuroreport (2001) [Pubmed]
  12. The C-terminal juxtamembrane region of the delta 2 glutamate receptor controls its export from the endoplasmic reticulum. Matsuda, S., Hannen, R., Matsuda, K., Yamada, N., Tubbs, T., Yuzaki, M. Eur. J. Neurosci. (2004) [Pubmed]
  13. The Lurcher mutation of an alpha-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid receptor subunit enhances potency of glutamate and converts an antagonist to an agonist. Taverna, F., Xiong, Z.G., Brandes, L., Roder, J.C., Salter, M.W., MacDonald, J.F. J. Biol. Chem. (2000) [Pubmed]
  14. Survival of interneurons and parallel fiber synapses in a cerebellar cortex deprived of Purkinje cells: studies in the double mutant mouse Grid2Lc/+;Bax(-/-). Zanjani, S.H., Selimi, F., Vogel, M.W., Haeberlé, A.M., Boeuf, J., Mariani, J., Bailly, Y.J. J. Comp. Neurol. (2006) [Pubmed]
  15. Altered intracellular localization of the glutamate receptor channel delta 2 subunit in weaver and reeler Purkinje cells. Takayama, C., Nakagawa, S., Watanabe, M., Kurihara, H., Mishina, M., Inoue, Y. Brain Res. (1997) [Pubmed]
  16. Delphilin: a novel PDZ and formin homology domain-containing protein that synaptically colocalizes and interacts with glutamate receptor delta 2 subunit. Miyagi, Y., Yamashita, T., Fukaya, M., Sonoda, T., Okuno, T., Yamada, K., Watanabe, M., Nagashima, Y., Aoki, I., Okuda, K., Mishina, M., Kawamoto, S. J. Neurosci. (2002) [Pubmed]
  17. Developmental changes in expression and distribution of the glutamate receptor channel delta 2 subunit according to the Purkinje cell maturation. Takayama, C., Nakagawa, S., Watanabe, M., Mishina, M., Inoue, Y. Brain Res. Dev. Brain Res. (1996) [Pubmed]
  18. Bax inactivation in lurcher mutants rescues cerebellar granule cells but not purkinje cells or inferior olivary neurons. Selimi, F., Vogel, M.W., Mariani, J. J. Neurosci. (2000) [Pubmed]
  19. Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development. Hashimoto, K., Ichikawa, R., Takechi, H., Inoue, Y., Aiba, A., Sakimura, K., Mishina, M., Hashikawa, T., Konnerth, A., Watanabe, M., Kano, M. J. Neurosci. (2001) [Pubmed]
  20. The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor delta 2 and epsilon subunits. Hironaka, K., Umemori, H., Tezuka, T., Mishina, M., Yamamoto, T. J. Biol. Chem. (2000) [Pubmed]
  21. Rescue of abnormal phenotypes of the delta2 glutamate receptor-null mice by mutant delta2 transgenes. Hirai, H., Miyazaki, T., Kakegawa, W., Matsuda, S., Mishina, M., Watanabe, M., Yuzaki, M. EMBO Rep. (2005) [Pubmed]
  22. Heteromer formation of delta2 glutamate receptors with AMPA or kainate receptors. Kohda, K., Kamiya, Y., Matsuda, S., Kato, K., Umemori, H., Yuzaki, M. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  23. Direct interaction of GluRdelta2 with Shank scaffold proteins in cerebellar Purkinje cells. Uemura, T., Mori, H., Mishina, M. Mol. Cell. Neurosci. (2004) [Pubmed]
  24. The delta2 glutamate receptor: 10 years later. Yuzaki, M. Neurosci. Res. (2003) [Pubmed]
  25. Identification and characterization of a novel Delphilin variant with an alternative N-terminus. Yamashita, T., Miyagi, Y., Ono, M., Ito, H., Watanabe, K., Sonoda, T., Tsuzuki, K., Ozawa, S., Aoki, I., Okuda, K., Mishina, M., Kawamoto, S. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  26. Control of synaptic connection by glutamate receptor delta2 in the adult cerebellum. Takeuchi, T., Miyazaki, T., Watanabe, M., Mori, H., Sakimura, K., Mishina, M. J. Neurosci. (2005) [Pubmed]
  27. Characterization of hippocampal theta rhythm in wild-type mice and glutamate receptor subunit delta2 mutant mice during eyeblink conditioning with a short trace interval. Takatsuki, K., Kawahara, S., Mishina, M., Kirino, Y. Brain Res. (2005) [Pubmed]
  28. Roles of diverse glutamate receptors in brain functions elucidated by subunit-specific and region-specific gene targeting. Mori, H., Mishina, M. Life Sci. (2003) [Pubmed]
  29. Membrane-proximal region of glutamate receptor delta2 subunit is critical for long-term depression and interaction with protein interacting with C kinase 1 in a cerebellar Purkinje neuron. Yawata, S., Tsuchida, H., Kengaku, M., Hirano, T. J. Neurosci. (2006) [Pubmed]
  30. Spectrin mutations cause spinocerebellar ataxia type 5. Ikeda, Y., Dick, K.A., Weatherspoon, M.R., Gincel, D., Armbrust, K.R., Dalton, J.C., Stevanin, G., Dürr, A., Zühlke, C., Bürk, K., Clark, H.B., Brice, A., Rothstein, J.D., Schut, L.J., Day, J.W., Ranum, L.P. Nat. Genet. (2006) [Pubmed]
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