Metabotropic glutamate receptor 8

Glutamate receptor, metabotropic 8

Identifiers

GRM8 ; GLUR8; GPRC1H; MGLUR8; mGlu8

External IDs

OMIM: 601116 MGI: 1351345 HomoloGene: 654 IUPHAR: 296 ChEMBL: 3228 GeneCards: GRM8 Gene

Gene ontology
Molecular function	• group III metabotropic glutamate receptor activity • G-protein coupled receptor activity • glutamate receptor activity
Cellular component	• plasma membrane • integral component of plasma membrane • presynaptic membrane
Biological process	• adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway • visual perception • sensory perception of smell • negative regulation of cAMP biosynthetic process • regulation of synaptic transmission, glutamatergic
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 7:
126.44 – 127.25 Mb

Chr 6:
27.28 – 28.14 Mb

PubMed search

Metabotropic glutamate receptor 8 is a protein that in humans is encoded by the GRM8 gene.^[1]^[2]

Function

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternative splice variants of GRM8 have been described but their full-length nature has not been determined.^[2]

Ligands

(S)-3,4-DCPG: agonist^[3]

Model organisms

Model organisms have been used in the study of GRM8 function. A conditional knockout mouse line called Grm8^{tm2a(KOMP)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[4] Male and female animals underwent a standardized phenotypic screen^[5] to determine the effects of deletion.^[6]^[7]^[8]^[9] Additional screens performed: - In-depth immunological phenotyping^[10]

*Grm8* knockout mouse phenotype
Characteristic	Phenotype
All data available at.^[5]^[10]
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal

References

↑ Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (Mar 1997). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics 31 (2): 230–3. doi:10.1006/geno.1996.0036. PMID 8824806.
1 2 "Entrez Gene: GRM8 glutamate receptor, metabotropic 8".
↑ Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE (2001). "(S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord". Neuropharmacology 40 (3): 311–8. doi:10.1016/S0028-3908(00)00169-6. PMID 11166323.
↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
1 2 "International Mouse Phenotyping Consortium".
↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".

Scherer SW, Soder S, Duvoisin RM, Huizenga JJ, Tsui LC (1997). "The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1". Genomics 44 (2): 232–6. doi:10.1006/geno.1997.4842. PMID 9299241.
Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, Johnson BG, Schoepp DD, Belagaje RM (1998). "Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells". Brain Res. Mol. Brain Res. 53 (1–2): 88–97. doi:10.1016/S0169-328X(97)00277-5. PMID 9473604.
Malherbe P, Kratzeisen C, Lundstrom K, Richards JG, Faull RL, Mutel V (1999). "Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8". Brain Res. Mol. Brain Res. 67 (2): 201–10. doi:10.1016/S0169-328X(99)00050-9. PMID 10216218.
Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE (2001). "(S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord". Neuropharmacology 40 (3): 311–8. doi:10.1016/S0028-3908(00)00169-6. PMID 11166323.
Enz R (2002). "The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7". FEBS Lett. 514 (2–3): 184–8. doi:10.1016/S0014-5793(02)02361-X. PMID 11943148.
Tang Z, El Far O, Betz H, Scheschonka A (2006). "Pias1 interaction and sumoylation of metabotropic glutamate receptor 8". J. Biol. Chem. 280 (46): 38153–9. doi:10.1074/jbc.M508168200. PMID 16144832.
Kobayashi Y, Akiyoshi J, Kanehisa M, Ichioka S, Tanaka Y, Tsuru J, Hanada H, Kodama K, Isogawa K, Tsutsumi T (2007). "Lack of polymorphism in genes encoding mGluR 7, mGluR 8, GABA(A) receptor alfa-6 subunit and nociceptin/orphanin FQ receptor and panic disorder". Psychiatr. Genet. 17 (1): 9. doi:10.1097/YPG.0b013e32801118bc. PMID 17167337.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

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Metabotropic glutamate receptor 8

Function

Ligands

See also

Model organisms

References

Further reading