Metabotropic glutamate receptor 8

GRM8
Identifiers
Aliases	GRM8, GLUR8, GPRC1H, MGLUR8, mGlu8, glutamate metabotropic receptor 8
External IDs	OMIM: 601116 MGI: 1351345 HomoloGene: 654 GeneCards: GRM8
Gene location (Human)
Chr.	Chromosome 7 (human)[1]
End	127,253,093 bp[1]
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)[2]
End	28,135,177 bp[2]
RNA expression pattern
	Top expressed in
	oocyte; ; prefrontal cortex; ; Brodmann area 9; ; corpus callosum; ; cingulate gyrus; ; putamen; ; caudate nucleus; ; hypothalamus; ; sperm; ; rectum;
	Top expressed in
	ganglion cell layer; ; secondary oocyte; ; inner nuclear layer; ; superior frontal gyrus; ; outer nuclear layer; ; cerebellar cortex; ; pontine nuclei; ; primary motor cortex; ; supraoptic nucleus; ; superior colliculus;
	More reference expression data
	n/a
Gene ontology
Molecular function	glutamate receptor activity; G protein-coupled receptor activity; signal transducer activity;
Cellular component	integral component of membrane; integral component of plasma membrane; presynaptic membrane; membrane; plasma membrane;
Biological process	adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway; signal transduction; visual perception; response to stimulus; regulation of synaptic transmission, glutamatergic; G protein-coupled receptor signaling pathway; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; G protein-coupled glutamate receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	2918
	14823
	ENSG00000179603
	ENSMUSG00000024211
	O00222
	P47743
NM_000845; NM_001127323; NM_001371083; NM_001371084; NM_001371085;
	NM_001371086; NM_001371087; NM_001371088
	NM_008174; NM_001311072; NM_001361125
NP_000836; NP_001120795; NP_001358012; NP_001358013; NP_001358014;
	NP_001358015; NP_001358016; NP_001358017
	NP_001298001; NP_032200; NP_001348054
	Wikidata
View/Edit Human	View/Edit Mouse

Metabotropic glutamate receptor 8 is a protein that in humans is encoded by the GRM8 gene.[5][6]

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.[6]

Ligands

(S)-3,4-DCPG: agonist[7]
AZ12216052: positive allosteric modulator[8]

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.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15]

*Grm8* knockout mouse phenotype
Characteristic	Phenotype
All data available at.[10][15]
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

GRCh38: Ensembl release 89: ENSG00000179603 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000024211 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (January 1996). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics. 31 (2): 230–233. doi:10.1006/geno.1996.0036. PMID 8824806.
"Entrez Gene: GRM8 glutamate receptor, metabotropic 8".
Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE (March 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): 311–318. doi:10.1016/S0028-3908(00)00169-6. PMID 11166323. S2CID 2872874.
Duvoisin RM, Pfankuch T, Wilson JM, Grabell J, Chhajlani V, Brown DG, et al. (October 2010). "Acute pharmacological modulation of mGluR8 reduces measures of anxiety". Behavioural Brain Research. 212 (2): 168–173. doi:10.1016/j.bbr.2010.04.006. PMC 2892883. PMID 20385173.
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. S2CID 85911512.
"International Mouse Phenotyping Consortium".
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–263. doi:10.1038/474262a. PMID 21677718.
Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–464. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
"Infection and Immunity Immunophenotyping (3i) Consortium". Archived from the original on 2015-05-21. Retrieved 2015-05-19.

Scherer SW, Soder S, Duvoisin RM, Huizenga JJ, Tsui LC (September 1997). "The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1". Genomics. 44 (2): 232–236. doi:10.1006/geno.1997.4842. PMID 9299241.
Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, et al. (January 1998). "Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells". Brain Research. Molecular Brain Research. 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 (April 1999). "Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8". Brain Research. Molecular Brain Research. 67 (2): 201–210. doi:10.1016/S0169-328X(99)00050-9. PMID 10216218.
Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE (March 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): 311–318. doi:10.1016/S0028-3908(00)00169-6. PMID 11166323. S2CID 2872874.
Enz R (March 2002). "The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7". FEBS Letters. 514 (2–3): 184–188. doi:10.1016/S0014-5793(02)02361-X. PMID 11943148. S2CID 44474808.
Tang Z, El Far O, Betz H, Scheschonka A (November 2005). "Pias1 interaction and sumoylation of metabotropic glutamate receptor 8". The Journal of Biological Chemistry. 280 (46): 38153–38159. doi:10.1074/jbc.M508168200. PMID 16144832.
Kobayashi Y, Akiyoshi J, Kanehisa M, Ichioka S, Tanaka Y, Tsuru J, et al. (February 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". Psychiatric Genetics. 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.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000179603 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000024211 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8824806-5] Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (January 1996). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics. 31 (2): 230–233. doi:10.1006/geno.1996.0036. PMID 8824806.

[entrez-6] "Entrez Gene: GRM8 glutamate receptor, metabotropic 8".

[pmid11166323-7] Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE (March 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): 311–318. doi:10.1016/S0028-3908(00)00169-6. PMID 11166323. S2CID 2872874.

[pmid20385173-8] Duvoisin RM, Pfankuch T, Wilson JM, Grabell J, Chhajlani V, Brown DG, et al. (October 2010). "Acute pharmacological modulation of mGluR8 reduces measures of anxiety". Behavioural Brain Research. 212 (2): 168–173. doi:10.1016/j.bbr.2010.04.006. PMC 2892883. PMID 20385173.

[mgp_reference-9] 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. S2CID 85911512.

[IMPCsearch_ref-10] "International Mouse Phenotyping Consortium".

[pmid21677750-11] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-12] Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–263. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-13] Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.

[pmid23870131-14] White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–464. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.

[iii_ref-15] "Infection and Immunity Immunophenotyping (3i) Consortium". Archived from the original on 2015-05-21. Retrieved 2015-05-19.

Metabotropic glutamate receptor 8

Function

Ligands

See also

Model organisms

References

Further reading