GRIK1
Glutamate receptor, ionotropic, kainate 1,also known asGRIK1,is aproteinthat in humans is encoded by theGRIK1gene.[5]
Function
[edit]This gene encodes one of the manyionotropic glutamate receptor(GluR) subunits that function as aligand-gated ion channel.The specific GluR subunit encoded by this gene is of thekainate receptorsubtype. Receptor assembly and intracellular trafficking of ionotropic glutamate receptors are regulated byRNA editingandalternative splicing.These receptors mediateexcitatory neurotransmissionand are critical for normalsynaptic function.Two alternatively spliced transcript variants that encode different isoforms have been described. Exons of this gene are interspersed with exons from the C21orf41 gene, which is transcribed in the same orientation as this gene but does not seem to encode a protein.[5]
Interactions
[edit]GRIK1 has been shown tointeractwithDLG4,[6]PICK1[6]andSDCBP.[6]
RNA editing
[edit]Type
[edit]A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3, with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues, whereas ADAR3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site, with residues usually in a neighboring intron, but can be an exonic sequence. The region that base-pairs with the editing region is known as an Editing Complementary Sequence (ECS). ADARs bind interact directly with the dsRNA substrate via their double-stranded RNA binding domains. If an editing site occurs within a coding sequence, the result could be a codon change. This can lead to translation of a protein isoform due to a change in its primary protein structure. Therefore, editing can also alter protein function. A to I editing occurs in a noncoding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs( especially Alu repeats). The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus, among others.
Location
[edit]The pre-mRNA of GluR-5 is edited at one position at the Q/R site located at membrane region 2 (M2). There is a codon change as a result of editing. The codon change is (CAG) Glutamine (Q) to (CGG) an Arginine (R).[7] Like GluR-6 the ECS is located about 2000 nucleotides downstream of the editing site.[8]
Regulation
[edit]Editing of the Q/R site is development- and tissue-regulated. Editing in the spinal cord, corpus callosum, cerebellum is 50%, while editing in the Thalamus, amygdala, hippocampus is about 70%.
Consequences
[edit]Structure
[edit]Editing results in a change in amino acid in the second membrane domain of the receptor.
Function
[edit]The editing site is found within the second intracellular domain. It is thought that editing affects the permeability of the receptor to CA2+. Editing of the Q/R site is thought to reduce the permeability of the channel to Ca2+[7]
RNA editing of the Q/R site can effect inhibition of the channel by membrane fatty acids such asarachidonic acidanddocosahexaenoic acid[9]For Kainate receptors with only edited isoforms, these are strongly inhibited by these fatty acids. However, inclusion of just one nonedited subunit is enough to stop this inhibition(.[9]
See also
[edit]- Kainate receptor
- GRIK1 RNA editing
References
[edit]- ^abcGRCh38: Ensembl release 89: ENSG00000171189–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000022935–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.
- ^ab"Entrez Gene: GRIK1 glutamate receptor, ionotropic, kainate 1".
- ^abcHirbec, Hélène; Francis, Joanna C.; Lauri, Sari E.; Braithwaite, Steven P.; Coussen, Françoise; Mulle, Christophe; Dev, Kumlesh K.; Coutinho, Victoria; Meyer, Guido; Isaac, John T. R.; Collingridge, Graham L.; Henley, Jeremy M.; Couthino, Victoria (Feb 2003)."Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP".Neuron.37(4). United States: 625–38.doi:10.1016/S0896-6273(02)01191-1.ISSN0896-6273.PMC3314502.PMID12597860.
- ^abSeeburg PH, Single F, Kuner T, Higuchi M, Sprengel R (July 2001). "Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse".Brain Res.907(1–2): 233–43.doi:10.1016/S0006-8993(01)02445-3.PMID11430906.S2CID11969068.
- ^Herb A, Higuchi M, Sprengel R, Seeburg PH (March 1996)."Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences".Proc. Natl. Acad. Sci. U.S.A.93(5): 1875–80.Bibcode:1996PNAS...93.1875H.doi:10.1073/pnas.93.5.1875.PMC39875.PMID8700852.
- ^abWilding TJ, Fulling E, Zhou Y, Huettner JE (July 2008)."Amino Acid Substitutions in the Pore Helix of GluR6 Control Inhibition by Membrane Fatty Acids".J. Gen. Physiol.132(1): 85–99.doi:10.1085/jgp.200810009.PMC2442176.PMID18562501.
Further reading
[edit]- Nutt SL, Kamboj RK (1995). "RNA editing of human kainate receptor subunits".NeuroReport.5(18): 2625–9.doi:10.1097/00001756-199412000-00055.PMID7696618.
- Roche KW, Raymond LA, Blackstone C, Huganir RL (1994)."Transmembrane topology of the glutamate receptor subunit GluR6".J. Biol. Chem.269(16): 11679–82.doi:10.1016/S0021-9258(17)32623-6.PMID8163463.
- Gregor P, O'Hara BF, Yang X, Uhl GR (1994). "Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6".NeuroReport.4(12): 1343–6.doi:10.1097/00001756-199309150-00014.PMID8260617.
- Eubanks JH, Puranam RS, Kleckner NW, et al. (1993)."The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis".Proc. Natl. Acad. Sci. U.S.A.90(1): 178–82.Bibcode:1993PNAS...90..178E.doi:10.1073/pnas.90.1.178.PMC45623.PMID8419920.
- Potier MC, Dutriaux A, Lambolez B, et al. (1993). "Assignment of the human glutamate receptor gene GLUR5 to 21q22 by screening a chromosome 21 YAC library".Genomics.15(3): 696–7.doi:10.1006/geno.1993.1131.PMID8468067.
- Korczak B, Nutt SL, Fletcher EJ, et al. (1996). "cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration".Recept. Channels.3(1): 41–9.PMID8589992.
- Brakeman PR, Lanahan AA, O'Brien R, et al. (1997). "Homer: a protein that selectively binds metabotropic glutamate receptors".Nature.386(6622): 284–8.Bibcode:1997Natur.386..284B.doi:10.1038/386284a0.PMID9069287.S2CID4346579.
- Sander T, Hildmann T, Kretz R, et al. (1997). "Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene (GRIK1) polymorphism".Am. J. Med. Genet.74(4): 416–21.doi:10.1002/(SICI)1096-8628(19970725)74:4<416::AID-AJMG13>3.0.CO;2-L.PMID9259378.
- Clarke VR, Ballyk BA, Hoo KH, et al. (1997). "A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission".Nature.389(6651): 599–603.Bibcode:1997Natur.389..599C.doi:10.1038/39315.PMID9335499.S2CID4426839.
- Xiao B, Tu JC, Petralia RS, et al. (1998)."Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins".Neuron.21(4): 707–16.doi:10.1016/S0896-6273(00)80588-7.PMID9808458.S2CID16431031.
- Montague AA, Greer CA (1999). "Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb".J. Comp. Neurol.405(2): 233–46.doi:10.1002/(SICI)1096-9861(19990308)405:2<233::AID-CNE7>3.0.CO;2-A.PMID10023812.S2CID1317987.
- Bortolotto ZA, Clarke VR, Delany CM, et al. (1999). "Kainate receptors are involved in synaptic plasticity".Nature.402(6759): 297–301.Bibcode:1999Natur.402..297B.doi:10.1038/46290.PMID10580501.S2CID205051834.
- Barbon A, Barlati S (2000). "Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1".Cytogenet. Cell Genet.88(3–4): 236–9.doi:10.1159/000015558.PMID10828597.S2CID5850944.
- Hattori M, Fujiyama A, Taylor TD, et al. (2000)."The DNA sequence of human chromosome 21".Nature.405(6784): 311–9.Bibcode:2000Natur.405..311H.doi:10.1038/35012518.PMID10830953.
- Ango F, Prézeau L, Muller T, et al. (2001). "Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer".Nature.411(6840): 962–5.Bibcode:2001Natur.411..962A.doi:10.1038/35082096.PMID11418862.S2CID4417727.
- Shibata H, Joo A, Fujii Y, et al. (2002). "Association study of polymorphisms in the GluR5 kainate receptor gene (GRIK1) with schizophrenia".Psychiatr. Genet.11(3): 139–44.doi:10.1097/00041444-200109000-00005.PMID11702055.S2CID38356907.
- Hirbec H, Perestenko O, Nishimune A, et al. (2002)."The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs"(PDF).J. Biol. Chem.277(18): 15221–4.doi:10.1074/jbc.C200112200.PMID11891216.S2CID13732968.
- 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.PMID11943148.S2CID44474808.
- Hirbec H, Francis JC, Lauri SE, et al. (2003)."Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP".Neuron.37(4): 625–38.doi:10.1016/S0896-6273(02)01191-1.PMC3314502.PMID12597860.
- Ren Z, Riley NJ, Needleman LA, et al. (2004)."Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal".J. Biol. Chem.278(52): 52700–9.doi:10.1074/jbc.M309585200.PMID14527949.
External links
[edit]- GRIK1+protein,+humanat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.