Metabotropic glutamate receptor 1
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| Location (UCSC) | Chr 6: 146.03 – 146.44 Mb | Chr 10: 10.56 – 10.96 Mb | |||||||
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The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 (mGluR1) protein.[5][6][7]
Function
L-
cyclic AMP cascade but differ in their agonist selectivities. Alternative splice variants of the GRM1 gene have been described but their full-length nature has not been determined.[5]
A possible connection has been suggested between mGluRs and neuromodulators, as mGluR1 antagonists block adrenergic receptor activation in neurons.[8]
Studies with knockout mice
Mice lacking functional glutamate receptor 1 were reported in 1994. By
Morris watermaze test, an assay for learning abilities, those mice needed significantly more time to successfully complete the task.[9]
Clinical significance
Mutations in the GRM1 gene may contribute to melanoma susceptibility.[10] Antibodies against mGluR1 receptors cause cerebellar ataxia and impair long-term depression (LTDpathies) in the cerebellum.[11]
Ligands
In addition to the orthosteric site (the site where the endogenous ligand glutamate binds) at least two distinct
allosteric binding sites exist on the mGluR1.[12] A respectable number of potent and specific allosteric ligands – predominantly antagonists/inhibitors – has been developed in recent years, although no orthosteric subtype-selective ligands have yet been discovered (2008).[13]
- JNJ-16259685: highly potent, selective non-competitive antagonist[14]
- R-214,127 and [3H]-analog: high-affinity, selective allosteric inhibitor[15]
- YM-202,074: high-affinity, selective allosteric antagonist[16]
- YM-230,888: high-affinity, selective allosteric antagonist[17]
- YM-298,198 and [3H]-analog: selective non-competitive antagonist[18]
- FTIDC: highly potent and selective allosteric antagonist/inverse agonist[19]
- A-841,720: potent non-competitive antagonist; minor hmGluR5 binding[20]
- VU-71: potentiator[12]
- Fluorinated 9H-xanthene-9-carboxylic acid oxazol-2-yl-amides: orally available PAMs[21]
- Cyclothiazide: selective non-competitive antagonist of the mGluR1[22] (also AMPA potentiator and minor mGluR5 potentiator but not antagonist[23])
- Riluzole : selective non-competitive antagonist[24]
- Theanine : possible indirect inhibitor[25]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000152822 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019828 - 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.
- ^ a b "Entrez Gene: GRM1 glutamate receptor, metabotropic 1".
- S2CID 37222391.
- S2CID 28116484.
- PMID 19474170.
- S2CID 4256888.
- PMID 17609672.
- PMID 33754326.
- ^ S2CID 2719603.
- ^ based on a plain PubMed review
- S2CID 601322.
- PMID 12695537.
- S2CID 3236484.
- PMID 17597604.
- S2CID 15291494.
- S2CID 10065500.
- PMID 17016515.
- PMID 19233648.
- PMID 17095021.
- PMID 17095021.
- S2CID 3605151.
- PMID 15207710.
Further reading
- Bockaert J, Pin JP (April 1999). "Molecular tinkering of G protein-coupled receptors: an evolutionary success". The EMBO Journal. 18 (7): 1723–1729. PMID 10202136.
- King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection. 8 (5): 1347–1357. PMID 16697675.
- Desai MA, Burnett JP, Mayne NG, Schoepp DD (October 1995). "Cloning and expression of a human metabotropic glutamate receptor 1 alpha: enhanced coupling on co-transfection with a glutamate transporter". Molecular Pharmacology. 48 (4): 648–657. PMID 7476890.
- 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. PMID 8824806.
- Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF (March 1997). "Homer: a protein that selectively binds metabotropic glutamate receptors". Nature. 386 (6622): 284–288. S2CID 4346579.
- Stephan D, Bon C, Holzwarth JA, Galvan M, Pruss RM (1997). "Human metabotropic glutamate receptor 1: mRNA distribution, chromosome localization and functional expression of two splice variants". Neuropharmacology. 35 (12): 1649–1660. S2CID 37222391.
- Makoff AJ, Phillips T, Pilling C, Emson P (September 1997). "Expression of a novel splice variant of human mGluR1 in the cerebellum". NeuroReport. 8 (13): 2943–2947. S2CID 28116484.
- Francesconi A, Duvoisin RM (March 1998). "Role of the second and third intracellular loops of metabotropic glutamate receptors in mediating dual signal transduction activation". The Journal of Biological Chemistry. 273 (10): 5615–5624. PMID 9488690.
- Okamoto T, Sekiyama N, Otsu M, Shimada Y, Sato A, Nakanishi S, Jingami H (May 1998). "Expression and purification of the extracellular ligand binding region of metabotropic glutamate receptor subtype 1". The Journal of Biological Chemistry. 273 (21): 13089–13096. PMID 9582347.
- Snow BE, Hall RA, Krumins AM, Brothers GM, Bouchard D, Brothers CA, et al. (July 1998). "GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain". The Journal of Biological Chemistry. 273 (28): 17749–17755. PMID 9651375.
- Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD, et al. (October 1998). "Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins". Neuron. 21 (4): 707–716. S2CID 16431031.
- Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, et al. (October 1998). "Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors". Neuron. 21 (4): 717–726. S2CID 2851554.
- Ciruela F, Robbins MJ, Willis AC, McIlhinney RA (January 1999). "Interactions of the C terminus of metabotropic glutamate receptor type 1alpha with rat brain proteins: evidence for a direct interaction with tubulin". Journal of Neurochemistry. 72 (1): 346–354. S2CID 3923065.
- Robbins MJ, Ciruela F, Rhodes A, McIlhinney RA (June 1999). "Characterization of the dimerization of metabotropic glutamate receptors using an N-terminal truncation of mGluR1alpha". Journal of Neurochemistry. 72 (6): 2539–2547. S2CID 43073802.
- Mody N, Hermans E, Nahorski SR, Challiss RA (October 1999). "Inhibition of N-linked glycosylation of the human type 1alpha metabotropic glutamate receptor by tunicamycin: effects on cell-surface receptor expression and function". Neuropharmacology. 38 (10): 1485–1492. S2CID 31175440.
- Francesconi A, Duvoisin RM (May 2000). "Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain". Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 6185–6190. PMID 10823959.
- Ganesh S, Amano K, Yamakawa K (2000). "Assignment of the gene GRM1 coding for metabotropic glutamate receptor 1 to human chromosome band 6q24 by in situ hybridization". Cytogenetics and Cell Genetics. 88 (3–4): 314–315. S2CID 26499807.
- Ray K, Hauschild BC (November 2000). "Cys-140 is critical for metabotropic glutamate receptor-1 dimerization". The Journal of Biological Chemistry. 275 (44): 34245–34251. PMID 10945991.
- Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. PMID 11076863.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
External links
- "Metabotropic Glutamate Receptors: mGlu1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-12-05.
- Overview of all the structural information available in the PDB for UniProt: Q13255 (Metabotropic glutamate receptor 1) at the PDBe-KB.
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