Retinal G protein coupled receptor explained

RPE-retinal G protein-coupled receptor also known as RGR-opsin is a protein that in humans is encoded by the RGR gene.^{[1] [2]} RGR-opsin is a member of the rhodopsin-like receptor subfamily of GPCR. Like other opsins which bind retinaldehyde, it contains a conserved lysine residue in the seventh transmembrane domain.^{[3] [4]} RGR-opsin comes in different isoforms produced by alternative splicing.

Function

RGR-opsin preferentially binds all-trans-retinal, which is the dominant form in the dark adapted retina, upon light exposure it is isomerized to 11-cis-retinal.^[5] Therefore, RGR-opsin presumably acts as a photoisomerase to convert all-trans-retinal to 11-cis-retinal, similar to retinochrome in invertebrates. 11-cis-retinal is isomerized back within rhodopsin and the iodopsins in the rods and cones of the retina. RGR-opsin is exclusively expressed in tissue close to the rods and cones, the retinal pigment epithelium (RPE) and Müller cells.

Phylogeny

The RGR-opsins are restricted to the echinoderms, the hemichordates the craniates.^[6] The craniates are the taxon that contains mammals and with them humans. The RGR-opsins are one of the seven subgroups of the chromopsins. The other groups are the peropsins, the retinochromes, the nemopsins, the astropsins, the varropsins, and the gluopsins. The chromopsins are one of three subgroups of the tetraopsins (also known as RGR/Go or Group 4 opsins). The other groups are the neuropsins and the Go-opsins. The tetraopsins are one of the five major groups of the animal opsins, also known as type 2 opsins). The other groups are the ciliary opsins (c-opsins, cilopsins), the rhabdomeric opsins (r-opsins, rhabopsins), the xenopsins, and the nessopsins. Four of these subclades occur in Bilateria (all but the nessopsins).^[7] However, the bilaterian clades constitute a paraphyletic taxon without the opsins from the cnidarians.^{[8] [9]}

In the phylogeny above, Each clade contains sequences from opsins and other G protein-coupled receptors. The number of sequences and two pie charts are shown next to the clade. The first pie chart shows the percentage of a certain amino acid at the position in the sequences corresponding to position 296 in cattle rhodopsin. The amino acids are color-coded. The colors are red for lysine (K), purple for glutamic acid (E), orange for arginine (R), dark and mid-gray for other amino acids, and light gray for sequences that have no data at that position. The second pie chart gives the taxon composition for each clade, green stands for craniates, dark green for cephalochordates, mid green for echinoderms, brown for nematodes, pale pink for annelids, dark blue for arthropods, light blue for mollusks, and purple for cnidarians. The branches to the clades have pie charts, which give support values for the branches. The values are from right to left SH-aLRT/aBayes/UFBoot. The branches are considered supported when SH-aLRT ≥ 80%, aBayes ≥ 0.95, and UFBoot ≥ 95%. If a support value is above its threshold the pie chart is black otherwise gray.

Clinical significance

RGR-opsin may be associated with autosomal recessive and autosomal dominant retinitis pigmentosa (arRP and adRP, respectively).^[10]

Interactions

RGR-opsin has been shown to interact with KIAA1279.^[11]

Further reading

• Jiang M, Shen D, Tao L, Pandey S, Heller K, Fong HK . Alternative splicing in human retinal mRNA transcripts of an opsin-related protein . Experimental Eye Research . 60 . 4 . 401–406 . April 1995 . 7789419 . 10.1016/S0014-4835(05)80096-X .
• Shen D, Jiang M, Hao W, Tao L, Salazar M, Fong HK . A human opsin-related gene that encodes a retinaldehyde-binding protein . Biochemistry . 33 . 44 . 13117–13125 . November 1994 . 7947717 . 10.1021/bi00248a022 .
• Chen P, Lee TD, Fong HK . Interaction of 11-cis-retinol dehydrogenase with the chromophore of retinal g protein-coupled receptor opsin . The Journal of Biological Chemistry . 276 . 24 . 21098–21104 . June 2001 . 11274198 . 10.1074/jbc.M010441200 . free .
• Yang M, Fong HK . Synthesis of the all-trans-retinal chromophore of retinal G protein-coupled receptor opsin in cultured pigment epithelial cells . The Journal of Biological Chemistry . 277 . 5 . 3318–3324 . February 2002 . 11723126 . 10.1074/jbc.M108946200 . free .
• Bellingham J, Wells DJ, Foster RG . In silico characterisation and chromosomal localisation of human RRH (peropsin)--implications for opsin evolution . BMC Genomics . 4 . 1 . 3 . January 2003 . 12542842 . 149353 . 10.1186/1471-2164-4-3 . free .
• Tarttelin EE, Bellingham J, Bibb LC, Foster RG, Hankins MW, Gregory-Evans K, Gregory-Evans CY, Wells DJ, Lucas RJ . Expression of opsin genes early in ocular development of humans and mice . Experimental Eye Research . 76 . 3 . 393–396 . March 2003 . 12573668 . 10.1016/S0014-4835(02)00300-7 .
• Bernal S, Calaf M, Garcia-Hoyos M, Garcia-Sandoval B, Rosell J, Adan A, Ayuso C, Baiget M . Study of the involvement of the RGR, CRPB1, and CRB1 genes in the pathogenesis of autosomal recessive retinitis pigmentosa . Journal of Medical Genetics . 40 . 7 . 89e–89 . July 2003 . 12843338 . 1735523 . 10.1136/jmg.40.7.e89 .
• Zhu L, Imanishi Y, Filipek S, Alekseev A, Jastrzebska B, Sun W, Saperstein DA, Palczewski K . Autosomal recessive retinitis pigmentosa and E150K mutation in the opsin gene . The Journal of Biological Chemistry . 281 . 31 . 22289–22298 . August 2006 . 16737970 . 1618956 . 10.1074/jbc.M602664200 . free .
• Lin MY, Kochounian H, Moore RE, Lee TD, Rao N, Fong HK . Deposition of exon-skipping splice isoform of human retinal G protein-coupled receptor from retinal pigment epithelium into Bruch's membrane . Molecular Vision . 13 . 1203–1214 . July 2007 . 17679941 .

Notes and References

1. Chen XN, Korenberg JR, Jiang M, Shen D, Fong HK . Localization of the human RGR opsin gene to chromosome 10q23 . Human Genetics . 97 . 6 . 720–722 . June 1996 . 8641686 . 10.1007/BF02346179 . 6086858 .
2. Web site: Entrez Gene: RGR retinal G protein coupled receptor.
3. Jiang M, Pandey S, Fong HK . An opsin homologue in the retina and pigment epithelium . Investigative Ophthalmology & Visual Science . 34 . 13 . 3669–3678 . December 1993 . 8258527 .
4. Shen D, Jiang M, Hao W, Tao L, Salazar M, Fong HK . A human opsin-related gene that encodes a retinaldehyde-binding protein . Biochemistry . 33 . 44 . 13117–13125 . November 1994 . 7947717 . 10.1021/bi00248a022 .
5. Hao W, Fong HK . The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium . The Journal of Biological Chemistry . 274 . 10 . 6085–6090 . March 1999 . 10037690 . 10.1074/jbc.274.10.6085 . free .
6. Gühmann M, Porter ML, Bok MJ . The Gluopsins: Opsins without the Retinal Binding Lysine . Cells . 11 . 15 . 2441 . August 2022 . 35954284 . 9368030 . 10.3390/cells11152441 . free . Material was copied and adapted from this source, which is available under a Creative Commons Attribution 4.0 International License.
7. The last common ancestor of most bilaterian animals possessed at least 9 opsins . Genome Biology and Evolution . evw248 . 26 October 2016 . 27797948 . 5521729 . 10.1093/gbe/evw248 . free . Ramirez M, Pairett A, Pankey M, Serb J, Speiser D, Swafford A, Oakley T .
8. Porter ML, Blasic JR, Bok MJ, Cameron EG, Pringle T, Cronin TW, Robinson PR . Shedding new light on opsin evolution . Proceedings. Biological Sciences . 279 . 1726 . 3–14 . January 2012 . 22012981 . 3223661 . 10.1098/rspb.2011.1819 .
9. Liegertová M, Pergner J, Kozmiková I, Fabian P, Pombinho AR, Strnad H, Pačes J, Vlček Č, Bartůněk P, Kozmik Z . Cubozoan genome illuminates functional diversification of opsins and photoreceptor evolution . Scientific Reports . 5 . 11885 . July 2015 . 26154478 . 5155618 . 10.1038/srep11885 . 2015NatSR...511885L .
10. Morimura H, Saindelle-Ribeaudeau F, Berson EL, Dryja TP . Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa . Nature Genetics . 23 . 4 . 393–394 . December 1999 . 10581022 . 10.1038/70496 . 35176366 .
11. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–1178 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . Huda Zoghbi . 2005Natur.437.1173R .