The Endogenous Chromophore of Retinal G Protein-coupled Receptor Opsin from the Pigment Epithelium

Hao, Wenshan; Fong, Henry K. W.

doi:10.1074/jbc.274.10.6085

Cited by 112 publications

(89 citation statements)

References 32 publications

(37 reference statements)

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“…Melanopsin is one of four opsins expressed outside the photoreceptor layer in human and mouse retinas, the other three being retinal G-protein-coupled receptor (RGR), peropsin, and encephalopsin. RGR is found predominantly in intracellular membranes of the RPE and Müller cells (Pandey et al, 1994) and functions as a photoisomerase (Hao and Fong, 1999). Peropsin is found within the microvilli of RPE cells, and its f unction is unknown (Hui et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

A Novel Human Opsin in the Inner Retina

et al. 2000

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Here we report the identification of a novel human opsin, melanopsin, that is expressed in cells of the mammalian inner retina. The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22. This chromosomal localization and gene structure differs significantly from that of other human opsins that typically have four to seven exons. A survey of 26 anatomical sites indicates that, in humans, melanopsin is expressed only in the eye. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas. Notably, expression is not observed in retinal photoreceptor cells, the opsin-containing cells of the outer retina that initiate vision. The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsinpositive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.

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Section: Discussionmentioning

confidence: 99%

A Novel Human Opsin in the Inner Retina

et al. 2000

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“…It is widely accepted that tissues other than photoreceptor organs, eyes, and pineal organs contain less 11-cis retinal that binds to opsin to form a photosensitive G protein-coupled pigment because 11-cis retinoids are generated by enzymes specifically present in the photoreceptor organs, i.e., photoisomerase retinochrome/retinal G proteincoupled receptor (RGR), and/or retinal pigment epitheliumspecific protein 65 kDa (RPE65) (11,12,24,25). Accordingly, one of the most important requirements for functioning of an opsin in extraocular tissues is that it forms photosensitive pigments with the other retinal isomers.…”

Section: -Cis Retinal Binding Ability Of Mosopn3mentioning

confidence: 99%

“…In addition to these bilaterian opsins, we discovered a G s -coupled opsin in the visual cells of prebilaterian jellyfish (5). In contrast to these opsins, the members of the retinochrome and peropsin groups preferentially bind all-trans retinal, and light absorption causes all-trans to 11-cis isomerization (8,(11)(12)(13). Therefore, the members of these two groups are considered to be retinal photoisomerases that produce 11-cis retinal.…”

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confidence: 99%

Homologs of vertebrate Opn3 potentially serve as a light sensor in nonphotoreceptive tissue

Koyanagi

Takada

Nagata

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

142

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Most opsins selectively bind 11-cis retinal as a chromophore to form a photosensitive pigment, which underlies various physiological functions, such as vision and circadian photoentrainment. Recently, opsin 3 (Opn3), originally called encephalopsin or panopsin, and its homologs were identified in various tissues including brain, eye, and liver in both vertebrates and invertebrates, including human. Because Opn3s are mainly expressed in tissues that are not considered to contain sufficient amounts of 11-cis retinal to form pigments, the photopigment formation ability of Opn3 has been of interest. Here, we report the successful expression of Opn3 homologs, pufferfish teleost multiple tissue opsin (PufTMT) and mosquito Opn3 (MosOpn3) and show that these proteins formed functional photopigments with 11-cis and 9-cis retinals. The PufTMT-and MosOpn3-based pigments have absorption maxima in the blue-to-green region and exhibit a bistable nature. These Opn3 homolog-based pigments activate G i -type and G o -type G proteins light dependently, indicating that they potentially serve as light-sensitive G i /G o -coupled receptors. We also demonstrated that mammalian cultured cells transfected with the MosOpn3 or PufTMT became light sensitive without the addition of 11-cis retinal and the photosensitivity retained after the continuous light exposure, showing a reusable pigment formation with retinal endogenously contained in culture medium. Interestingly, we found that the MosOpn3 also acts as a light sensor when constituted with 13-cis retinal, a ubiquitously present retinal isomer. Our findings suggest that homologs of vertebrate Opn3 might function as photoreceptors in various tissues; furthermore, these Opn3s, particularly the mosquito homolog, could provide a promising optogenetic tool for regulating cAMP-related G protein-coupled receptor signalings.rhodopsin | phototransduction | nonvisual photoreception | opsin diversity M ost opsins bind 11-cis retinal as a chromophore to form a photosensitive pigment (opsin-based pigment) that serves as a light-sensitive G protein-coupled receptor (GPCR). The 11-cis to all-trans isomerization of the chromophore in an opsinbased pigment upon light absorption triggers G protein activation (1-4), and the photoreception of the opsin-based pigment initiates vision and nonvisual functions, including circadian entrainment and pupil responses. Several thousand opsins have been identified, and they are phylogenetically classified into eight groups based on the members that have existed early in animal evolution (5). The phylogenetic classification of each opsin also roughly corresponds to its molecular function. The G t -coupled opsin group contains vertebrate visual pigments, which activate transducin (G t )-type G proteins, and some nonvisual pigments, such as pinopsin, VA-opsin, parapinopsin, and parietopsin (1-4). The G q -coupled opsin group is composed of the visual pigments from many invertebrates, such as insects and cephalopods, and the vertebrate opsin 4 (Opn4) homologs (melanops...

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“…Exposing RGR to light induces photoisomerization of the all-trans-RAL to 11-cis-RAL (15). Unlike rhodopsin, RGR does not readily release its bound chromophore following photoisomerization (15).…”

Section: Charles Kenneth Feldman and Jules And Doris Stein Research Tmentioning

confidence: 99%

“…RGR is 20.4% identical to mammalian rhodopsin and 23.6% identical to retinochrome, an opsin homolog in squid that regenerates visual chromophore by photoisomerization (14). Dark-adapted RGR contains predominantly all-trans-RAL, coupled via a Schiff base to a Lys residue, similar to rhodopsin (15). RGR has absorption maxima ( max ) at 370 and 469 nm from the unpro-* This work was supported, in whole or in part, by National Institutes of Health Grant NEI R01-EY01584.…”

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confidence: 99%

Retinal Pigment Epithelium-Retinal G Protein Receptor-Opsin Mediates Light-dependent Translocation of All-trans-retinyl Esters for Synthesis of Visual Chromophore in Retinal Pigment Epithelial Cells

Radu¹,

Hu²,

Peng³

et al. 2008

Journal of Biological Chemistry

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Visual perception begins with the absorption of a photon by an opsin pigment, inducing isomerization of its 11-cis-retinaldehyde chromophore. After a brief period of activation, the resulting all-trans-retinaldehyde dissociates from the opsin apoprotein rendering it insensitive to light. Restoring light sensitivity to apo-opsin requires thermal re-isomerization of alltrans-retinaldehyde to 11-cis-retinaldehyde via an enzyme pathway called the visual cycle in retinal pigment epithelial (RPE) cells. Vertebrates can see over a 10 8 -fold range of background illumination. This implies that the visual cycle can regenerate a visual chromophore over a similarly broad range. However, nothing is known about how the visual cycle is regulated. Here we show that RPE cells, functionally or physically separated from photoreceptors, respond to light by mobilizing all-trans-retinyl esters. These retinyl esters are substrates for the retinoid isomerase and hence critical for regenerating visual chromophore. We show in knock-out mice and by RNA interference in human RPE cells that this mobilization is mediated by a protein called "RPE-retinal G protein receptor" (RGR) opsin. These data establish that RPE cells are intrinsically sensitive to light. Finally, we show that in the dark, RGR-opsin inhibits lecithin:retinol acyltransferase and all-trans-retinyl ester hydrolase in vitro and that this inhibition is released upon exposure to light. The results of this study suggest that RGR-opsin mediates light-dependent translocation of all-trans-retinyl esters from a storage pool in lipid droplets to an "isomerase pool" in membranes of the endoplasmic reticulum. This translocation permits insoluble all-trans-retinyl esters to be utilized as substrate for the synthesis of a new visual chromophore.The opsins include a group of light-sensitive G protein-coupled receptors. The ligand for most opsins is 11-cis-retinaldehyde (11-cis-RAL), 3 which is covalently coupled to a Lys residue in the opsins as a Schiff base. Absorption of a photon by most photoreceptor opsins isomerizes the 11-cis-RAL to all-transretinaldehyde (all-trans-RAL), inducing a conformational change that activates the G protein (transducin) and begins the visual transduction cascade (1). In the case of vertebrate photoreceptor opsins (rhodopsin and the cone opsins), the Schiff base is hydrolyzed and all-trans-RAL dissociates following photoisomerization. Restoration of light sensitivity to the resulting apo-opsin requires thermal re-isomerization of all-trans-RAL to 11-cis-RAL via a multistep enzyme pathway called the visual cycle in cells of the adjacent retinal pigment epithelium (RPE) (2) (Fig. 1). In contrast, all-trans-RAL remains covalently bound to many invertebrate opsins following photoisomerization. Here, the bound all-trans-RAL is re-isomerized in situ back to 11-cis-RAL by absorption of a second photon through a process called photoregeneration (3)(4)(5). Besides rhodopsin and the cone opsins, vertebrates contain several "nonvisual" opsins with sequence similarity...

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The Endogenous Chromophore of Retinal G Protein-coupled Receptor Opsin from the Pigment Epithelium

Cited by 112 publications

References 32 publications

A Novel Human Opsin in the Inner Retina

A Novel Human Opsin in the Inner Retina

Homologs of vertebrate Opn3 potentially serve as a light sensor in nonphotoreceptive tissue

Retinal Pigment Epithelium-Retinal G Protein Receptor-Opsin Mediates Light-dependent Translocation of All-trans-retinyl Esters for Synthesis of Visual Chromophore in Retinal Pigment Epithelial Cells

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