GRID2

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This article is about a protein. For a racing video game, see Grid 2.
Glutamate receptor, ionotropic, delta 2
Identifiers
Symbols GRID2 ; GluD2
External IDs OMIM602368 MGI95813 HomoloGene74399 IUPHAR: GluD2 GeneCards: GRID2 Gene
RNA expression pattern
PBB GE GRID2 221364 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2895 14804
Ensembl ENSG00000152208 ENSMUSG00000071424
UniProt O43424 Q61625
RefSeq (mRNA) NM_001510 NM_008167
RefSeq (protein) NP_001501 NP_032193
Location (UCSC) Chr 4:
93.23 – 94.7 Mb
Chr 6:
63.26 – 64.67 Mb
PubMed search [1] [2]

Glutamate receptor, ionotropic, delta 2, also known as GluD2, GluRδ2, or δ2, is a protein that in humans is encoded by the GRID2 gene.[1][2]

δ2 proteins are subunits that form excitatory ligand-gated ion channels and possess 14-24% sequence homology with AMPA, kainate, and NMDA subunits, but, despite their name, do not actually bind glutamate or various other glutamate agonists.[3][4] They are considered orphan subunits and their endogenous ligand is unknown.[5] δ2-containing receptors are selectively/predominantly expressed in Purkinje cells in the cerebellum and play a role in synaptogenesis, synaptic plasticity, and motor coordination, as well as in apoptosis (see below).[3][4][5]

Function[edit]

Human glutamate receptor delta-2 (GRID2) is a relatively new member of the family of ionotropic glutamate receptors which are the predominant excitatory neurotransmitter receptors in the mammalian brain. GRID2 is a predicted 1,007 amino acid protein that shares 97% identity with the mouse homolog which is expressed selectively in cerebellar Purkinje cells. A point mutation in mouse GRID2, associated with the phenotype named 'lurcher', in the heterozygous state leads to ataxia and motor coordination deficits resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development.[6] Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. This strongly suggests a role for GRID2 in neuronal apoptosis.[1]

Pathology[edit]

A heterozygous deletion in GRID2 in humans causes a complicated spastic paraplegia with ataxia, frontotemporal dementia, and lower motor neuron involvement[7] whereas a homozygous beallelic deletion leads to a syndrome of cerebellar ataxia with marked developmental delay, pyramidal tract involvement [8] and tonic upgaze,[9] that can be classified as an ataxia with oculomotor apraxia (AOA).

Ligands[edit]

9-Aminoacridine, 9-tetrahydroaminoacridine, N1-dansyl-spermine, N1-dansyl-spermidine, and pentamidine have been shown to act as antagonists of δ2-containing receptors.[5]

Interactions[edit]

GRID2 has been shown to interact with GOPC,[10] GRIK2,[11] PTPN4[12] and GRIA1.[11]

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: GRID2 glutamate receptor, ionotropic, delta 2". 
  2. ^ Hu W, Zuo J, De Jager PL, Heintz N (January 1998). "The human glutamate receptor delta 2 gene (GRID2) maps to chromosome 4q22". Genomics 47 (1): 143–5. doi:10.1006/geno.1997.5108. PMID 9465309. 
  3. ^ a b Lomeli H, Sprengel R, Laurie DJ, et al. (January 1993). "The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family". FEBS Letters 315 (3): 318–22. doi:10.1016/0014-5793(93)81186-4. PMID 8422924. 
  4. ^ a b Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M (December 1993). "Selective expression of the glutamate receptor channel delta 2 subunit in cerebellar Purkinje cells". Biochemical and Biophysical Research Communications 197 (3): 1267–76. doi:10.1006/bbrc.1993.2614. PMID 7506541. 
  5. ^ a b c Williams K, Dattilo M, Sabado TN, Kashiwagi K, Igarashi K (May 2003). "Pharmacology of delta2 glutamate receptors: effects of pentamidine and protons". The Journal of Pharmacology and Experimental Therapeutics 305 (2): 740–8. doi:10.1124/jpet.102.045799. PMID 12606689. 
  6. ^ Lalonde R, Botez MI, Joyal CC, Caumartin M (March 1992). "Motor abnormalities in lurcher mutant mice". Physiol. Behav. 51 (3): 523–5. doi:10.1016/0031-9384(92)90174-Z. PMID 1523229. 
  7. ^ Maier A, Klopocki E, Horn D, Tzschach A, Holm T, Meyer R, Meyer T (February 2014). "De novo partial deletion in GRID2 presenting with complicated spastic paraplegia". Muscle Nerve 49 (2): 289–92. doi:10.1002/mus.24096. PMID 24122788. 
  8. ^ Utine GE, Haliloğlu G, Salanci B, Çetinkaya A, Kiper PÖ, Alanay Y, Aktas D, Boduroğlu K, Alikaşifoğlu M (Jul 2013). "A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy". J Child Neurol. 28 (7): 926–32. doi:10.1177/0883073813484967. PMID 23611888. 
  9. ^ Hills LB, Masri A, Konno K, Kakegawa W, Lam AT, Lim-Melia E, Chandy N, Hill RS, Partlow JN, Al-Saffar M, Nasir R, Stoler JM, Barkovich AJ, Watanabe M, Yuzaki M, Mochida GH (Oct 2013). "Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans". Neurology 81 (16): 1378–86. doi:10.1212/WNL.0b013e3182a841a3. PMID 24078737. 
  10. ^ Yue, Zhenyu; Horton Antony; Bravin Monica; DeJager Philip L; Selimi Fekrije; Heintz Nathaniel (August 2002). "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice". Neuron (United States) 35 (5): 921–33. doi:10.1016/S0896-6273(02)00861-9. ISSN 0896-6273. PMID 12372286. 
  11. ^ a b Kohda, Kazuhisa; Kamiya Yoshinori; Matsuda Shinji; Kato Kunio; Umemori Hisashi; Yuzaki Michisuke (January 2003). "Heteromer formation of delta2 glutamate receptors with AMPA or kainate receptors". Brain Res. Mol. Brain Res. (Netherlands) 110 (1): 27–37. doi:10.1016/S0169-328X(02)00561-2. ISSN 0169-328X. PMID 12573530. 
  12. ^ Hironaka, K; Umemori H; Tezuka T; Mishina M; Yamamoto T (May 2000). "The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor delta 2 and epsilon subunits". J. Biol. Chem. (UNITED STATES) 275 (21): 16167–73. doi:10.1074/jbc.M909302199. ISSN 0021-9258. PMID 10748123. 

Further reading[edit]

  • Araki K, Meguro H, Kushiya E, et al. (1994). "Selective expression of the glutamate receptor channel delta 2 subunit in cerebellar Purkinje cells.". Biochem. Biophys. Res. Commun. 197 (3): 1267–76. doi:10.1006/bbrc.1993.2614. PMID 7506541. 
  • Hu W, Zuo J, De Jager PL, Heintz N (1998). "The human glutamate receptor delta 2 gene (GRID2) maps to chromosome 4q22.". Genomics 47 (1): 143–5. doi:10.1006/geno.1997.5108. PMID 9465309. 
  • "Toward a complete human genome sequence.". Genome Res. 8 (11): 1097–108. 1999. doi:10.1101/gr.8.11.1097. PMID 9847074. 
  • Roche KW, Ly CD, Petralia RS, et al. (1999). "Postsynaptic density-93 interacts with the delta2 glutamate receptor subunit at parallel fiber synapses.". J. Neurosci. 19 (10): 3926–34. PMID 10234023. 
  • Hironaka K, Umemori H, Tezuka T, et al. (2000). "The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor delta 2 and epsilon subunits.". J. Biol. Chem. 275 (21): 16167–73. doi:10.1074/jbc.M909302199. PMID 10748123. 
  • Miyagi Y, Yamashita T, Fukaya M, et al. (2002). "Delphilin: a novel PDZ and formin homology domain-containing protein that synaptically colocalizes and interacts with glutamate receptor delta 2 subunit.". J. Neurosci. 22 (3): 803–14. PMID 11826110. 
  • Ly CD, Roche KW, Lee HK, Wenthold RJ (2002). "Identification of rat EMAP, a delta-glutamate receptor binding protein.". Biochem. Biophys. Res. Commun. 291 (1): 85–90. doi:10.1006/bbrc.2002.6413. PMID 11829466. 
  • Yue Z, Horton A, Bravin M, et al. (2002). "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice.". Neuron 35 (5): 921–33. doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Kohda K, Kamiya Y, Matsuda S, et al. (2003). "Heteromer formation of delta2 glutamate receptors with AMPA or kainate receptors.". Brain Res. Mol. Brain Res. 110 (1): 27–37. doi:10.1016/S0169-328X(02)00561-2. PMID 12573530. 
  • Yap CC, Muto Y, Kishida H, et al. (2003). "PKC regulates the delta2 glutamate receptor interaction with S-SCAM/MAGI-2 protein.". Biochem. Biophys. Res. Commun. 301 (4): 1122–8. doi:10.1016/S0006-291X(03)00070-6. PMID 12589829. 
  • Sonoda T, Mochizuki C, Yamashita T, et al. (2006). "Binding of glutamate receptor delta2 to its scaffold protein, Delphilin, is regulated by PKA.". Biochem. Biophys. Res. Commun. 350 (3): 748–52. doi:10.1016/j.bbrc.2006.09.109. PMID 17027646.