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Delta Glutamate Receptor (GluD1, GluD2)

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

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Synonyms

GluD1; GluD2; GluRδ1; GluRδ2

Historical Background

The δ1 glutamate receptor (GluRδ1 and GluD1) and the δ2 glutamate receptor (GluRδ2 and GluD2) were cloned by homology screening in 1993 at the end of the “gold rush” for cloning of ionotropic glutamate receptor (iGluR) cDNA. They were regarded as orphan receptors for a long time since their endogenous ligands were unknown. GluD1 is highly expressed in hair cells of the auditory and vestibular systems in adult mice. Indeed, deletion of a gene encoding GluD1 (grid1) in mice leads to deficit in high-frequency hearing. In contrast, GluD2 is predominantly expressed in cerebellar Purkinje cells and deletion of a gene encoding GluD2 (grid2) results in cerebellar ataxia and characteristic phenotypes at parallel fiber (PF)–Purkinje cell synapses. Functionally, the long-term depression (LTD) of synaptic transmission, which is thought to underlie motor coordination and motor learning, is completely blunted. Morphologically,...

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References

  • Ady V, Perroy J, Tricoire L, Piochon C, Dadak S, Chen X, et al. Type 1 metabotropic glutamate receptor (mGlu1) trigger the gating of GluD2 delta glutamate receptors. EMBO Rep. 2014;15:103–9.

    Article  CAS  PubMed  Google Scholar 

  • Buckner RL. The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron. 2013;80:807–15.

    Article  CAS  PubMed  Google Scholar 

  • Coutelier M, Burglen L, Mundwiller E, Abada-Bendib M, Rodriguez D, Chantot-Bastaraud S, et al. GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia. Neurology. 2015;84:1751–9.

    Article  CAS  PubMed  Google Scholar 

  • Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, et al. Structural basis for integration of GluD receptors within synaptic organizer complexes. Science. 2016;353:295–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fallin MD, Lasseter VK, Avramopoulos D, Nicodemus KK, Wolyniec PS, McGrath JA, et al. Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios. Am J Hum Genet. 2005;77:918–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009;459:569–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo SZ, Huang K, Shi YY, Tang W, Zhou J, Feng GY, et al. A case-control association study between the GRID1 gene and schizophrenia in the Chinese Northern Han population. Schizophr Res. 2007;93:385–90.

    Article  PubMed  Google Scholar 

  • Hepp R, Hay YA, Aguado C, Lujan R, Dauphinot L, Potier MC, et al. Glutamate receptors of the delta family are widely expressed in the adult brain. Brain Struct Funct. 2015;220:2797–815.

    Article  CAS  PubMed  Google Scholar 

  • Hills LB, Masri A, Konno K, Kakegawa W, Lam AT, Lim-Melia E, et al. Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans. Neurology. 2013;81:1378–86.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirai H, Miyazaki T, Kakegawa W, Matsuda S, Mishina M, Watanabe M, et al. Rescue of abnormal phenotypes of the delta2 glutamate receptor-null mice by mutant delta2 transgenes. EMBO Rep. 2005;6:90–5.

    Article  CAS  PubMed  Google Scholar 

  • Kakegawa W, Miyazaki T, Hirai H, Motohashi J, Mishina M, Watanabe M, et al. Ca2+ permeability of the channel pore is not essential for the delta2 glutamate receptor to regulate synaptic plasticity and motor coordination. J Physiol. 2007a;579:729–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kakegawa W, Kohda K, Yuzaki M. The delta2 ‘ionotropic’ glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity. J Physiol. 2007b;584:89–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kakegawa W, Miyazaki T, Emi K, Matsuda K, Kohda K, Motohashi J, et al. Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRdelta2. J Neurosci. 2008;28:1460–8.

    Article  CAS  PubMed  Google Scholar 

  • Kakegawa W, Miyazaki T, Kohda K, Matsuda K, Emi K, Motohashi J, et al. The N-terminal domain of GluD2 (GluRdelta2) recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo. J Neurosci. 2009;29:5738–48.

    Article  CAS  PubMed  Google Scholar 

  • Kakegawa W, Miyoshi Y, Hamase K, Matsuda S, Matsuda K, Kohda K, et al. D-serine regulates cerebellar LTD and motor coordination through the delta2 glutamate receptor. Nat Neurosci. 2011;14:603–11.

    Article  CAS  PubMed  Google Scholar 

  • Kina S, Tezuka T, Kusakawa S, Kishimoto Y, Kakizawa S, Hashimoto K, et al. Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression. Eur J Neurosci. 2007;26:2269–78.

    Article  PubMed  Google Scholar 

  • Kohda K, Wang Y, Yuzaki M. Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties. Nat Neurosci. 2000;3:315–22.

    Article  CAS  PubMed  Google Scholar 

  • Kohda K, Kakegawa W, Matsuda S, Nakagami R, Kakiya N, Yuzaki M. The extreme C-terminus of GluRdelta2 is essential for induction of long-term depression in cerebellar slices. Eur J Neurosci. 2007;25:1357–62.

    Article  PubMed  Google Scholar 

  • Kohda K, Kakegawa W, Matsuda S, Yamamoto T, Hirano H, Yuzaki M. The δ2 glutamate receptor gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites. Proc Natl Acad Sci USA. 2013;110:E948–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Konno K, Matsuda K, Nakamoto C, Uchigashima M, Miyazaki T, Yamasaki M, Sakimura K, Yuzaki M, Watanabe M. Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum. J Neurosci. 2014;34:7412–24.

    Article  CAS  PubMed  Google Scholar 

  • Maier A, Klopocki E, Horn D, Tzschach A, Holm T, Meyer R, et al. De novo partial deletion in GRID2 presenting with complicated spastic paraplegia. Muscle Nerve. 2014;49:289–92.

    Article  CAS  PubMed  Google Scholar 

  • Matsuda K, Yuzaki M. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci. 2011;33:1447–61.

    Article  PubMed  Google Scholar 

  • Matsuda K, Miura E, Miyazaki T, Kakegawa W, Emi K, Narumi S, et al. Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer. Science. 2010;328:363–8.

    Article  CAS  PubMed  Google Scholar 

  • Matsuda S, Launey T, Mikawa S, Hirai H. Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons. EMBO J. 2000;19:2765–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naur P, Hansen KB, Kristensen AS, Dravid SM, Pickering DS, Olsen L, et al. Ionotropic glutamate-like receptor delta2 binds D-serine and glycine. Proc Natl Acad Sci USA. 2007;104:14116–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith M, Spence MA, Flodman P. Nuclear and mitochondrial genome defects in autisms. Ann NY Acad Sci. 2009;1151:102–32.

    Article  CAS  PubMed  Google Scholar 

  • Treutlein J, Muhleisen TW, Frank J, Mattheisen M, Herms S, Ludwig KU, et al. Dissection of phenotype reveals possible association between schizophrenia and glutamate receptor delta 1 (GRID1) gene promoter. Schizophr Res. 2009;111:123–30.

    Article  PubMed  Google Scholar 

  • Utine GE, Haliloğlu G, Salanci B, Çetinkaya A, Kiper PÖ, Alanay Y, et al. A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy. J Child Neurol. 2013;28:926–32.

    Article  PubMed  Google Scholar 

  • Van Schil K, Meire F, Karlstetter M, Bauwens M, Verdin H, Coppieters F, et al. Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion. Genet Med. 2015;17:291–9.

    Article  CAS  PubMed  Google Scholar 

  • Yadav R, Rimerman R, Scofield MA, Dravid SM. Mutations in the transmembrane domain M3 generate spontaneously open orphan glutamate delta 1 receptor. Brain Res. 2011;1382:1–8.

    Article  CAS  PubMed  Google Scholar 

  • Yadav R, Gupta SC, Hillman BG, Bhatt JM, Stairs DJ, Dravid SM. Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. PLoS One. 2012;7:e32969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav R, Hillman BG, Gupta SC, Suryavanshi P, Bhatt JM, Pavuluri R, Stairs DJ, Dravid SM. Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning. PLoS One. 2013;8:e60785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamasaki M, Miyazaki T, Azechi H, Abe M, Natsume R, Hagiwara T, et al. Glutamate receptor delta2 is essential for input pathway-dependent regulation of synaptic AMPAR contents in cerebellar Purkinje cells. J Neurosci. 2011;31:3362–74.

    Article  CAS  PubMed  Google Scholar 

  • Yuzaki M. Delta receptors. In: Gereau RW, Swanson GT, editors. The glutamate receptors. Totowa: Humana; 2008.

    Google Scholar 

  • Zuo J, De Jager PL, Takahashi KA, Jiang W, Linden DJ, Heintz N. Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene. Nature. 1997;388:769–73.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurophysiology, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan

    Kazuhisa Kohda, Wataru Kakegawa & Michisuke Yuzaki

  2. Department of Physiology, St. Marianna University School of Medicine, 2-16-1, Sugao, 216-8551, Kawasaki, Kanagawa, Japan

    Kazuhisa Kohda

Authors
  1. Kazuhisa Kohda
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  2. Wataru Kakegawa
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  3. Michisuke Yuzaki
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Corresponding author

Correspondence to Kazuhisa Kohda .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

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Kohda, K., Kakegawa, W., Yuzaki, M. (2016). Delta Glutamate Receptor (GluD1, GluD2). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_642-1

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  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_642-1

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  • Online ISBN: 978-1-4614-6438-9

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