GRID2

This article is about a protein. For a racing video game, see Grid 2.
Glutamate receptor, ionotropic, delta 2
Identifiers
SymbolsGRID2 ; GluD2
External IDsOMIM: 602368 MGI: 95813 HomoloGene: 74399 IUPHAR: 449 GeneCards: GRID2 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez289514804
EnsemblENSG00000152208ENSMUSG00000071424
UniProtO43424Q61625
RefSeq (mRNA)NM_001286838NM_008167
RefSeq (protein)NP_001273767NP_032193
Location (UCSC)Chr 4:
93.23 – 94.7 Mb		Chr 6:
63.26 – 64.67 Mb
PubMed search

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

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

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

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

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

See also

References

  1. ↑ 1.0 1.1 "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. ↑ 3.0 3.1 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. ↑ 4.0 4.1 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. ↑ 5.0 5.1 5.2 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. ↑ 11.0 11.1 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

  • 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.