Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Muller Glial Cells.
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ABSTRACT:
SUBMITTER: Morshedian A
PROVIDER: S-EPMC6586478 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Project description:Purpose:Retinal G protein-coupled receptor (RGR) mRNA is transcribed in the outer nuclear layer of human retinas; however, it is not known whether the RGR gene is expressed in the rod or cone photoreceptors. In this study, we investigate broader expression of the normal RGR isoform in photoreceptors of human and bovine retinas. Methods:We produced and validated a rabbit polyclonal antipeptide antibody (DE15) that is directed against a peptide sequence (SSLLRRWPHGSEGC) partly conserved in RGR across several species. Bovine and human retina sections were analyzed with immunohistochemical and double-label immunofluorescent staining. Results:The DE15 antibody bound specifically to overexpressed recombinant RGR, purified RGR from bovine RPE, and RGR in crude RPE membrane extracts without cross-reaction to other proteins. Immunostaining of diurnal bovine and human retinas with DE15 showed labeling of long-wavelength-sensitive and short-wavelength-sensitive cone photoreceptors and some retinal ganglion cells in both species. Strong labeling with DE15 was detected throughout the cone photoreceptor, including the outer segment, inner segment, cell body, axon, and cone pedicle, while rod outer segments were negative. Immunostaining for human exon-6-skipping RGR (RGR-d) was found primarily at the tips of the outer segment of the cones. Conclusions:The results indicate that the cone photoreceptors in these mammals express a nonvisual opsin of the Go/RGR or tetraopsin group. RGR and the visual pigments are predominantly colocalized in the cone outer segment, which suggests functional interaction among these opsins. Human cone photoreceptors may also contain normal RGR and the aberrant RGR-d splice isoform.
| S-EPMC6031102 | biostudies-literature
Project description:The chicken retina contains rhodopsin (a rod visual pigment) and four kinds of cone visual pigments. The primary structures of chicken red (iodopsin) and rhodopsin have been determined previously. Here we report isolation of three cDNA clones encoding additional pigments from a chicken retinal cDNA library. Based on the partial amino acid sequences of the purified chicken visual pigments together with their biochemical and spectral properties, we have identified these clones as encoding the chicken green, blue, and violet visual pigments. Chicken violet was very similar to human blue not only in absorption maximum (chicken violet, 415 nm; human blue, 419 nm) but also in amino acid sequence (80.6% identical). Interestingly, chicken green was more similar (71-75.1%) than any other known cone pigment (42.0-53.7%) to vertebrate rhodopsins. The fourth additional cone pigment, chicken blue, had relatively low similarity (39.3-54.6%) in amino acid sequence to those of the other vertebrate visual pigments. A phylogenetic tree of vertebrate visual pigments constructed on the basis of amino acid identity indicated that an ancestral visual pigment evolved first into four groups (groups L, S, M1, and M2), each of which includes one of the chicken cone pigments, and that group Rh including vertebrate rhodopsins diverged from group M2 later. Thus, it is suggested that the gene for scotopic vision (rhodopsin) has evolved out of that for photopic vision (cone pigments). The divergence of rhodopsin from cone pigments was accompanied by an increase in negative net charge of the pigment.
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Project description:In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.
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Project description:Fishes often have cone photoreceptors organized in lattice-like mosaic formations. In flatfishes, these lattices undergo dramatic changes during metamorphosis whereby a honeycomb mosaic of single cones in the larva is replaced by a square mosaic of single and double cones in the adult. The spatio-temporal dynamics of this transition are not well understood. Here, we describe the photoreceptors and mosaic formations that occur during the larva to juvenile transition of Atlantic halibut from the beginning of eye migration to its completion. To gauge the possibility of colour vision, visual pigments in juveniles were measured by microspectrophotometry and the opsin repertoire explored using bioinformatics. At the start of eye migration, the larva had a heterogeneous retina with honeycomb mosaic in the dorsonasal and ventrotemporal quadrants and a square mosaic in the ventronasal and dorsotemporal quadrants. By the end of metamorphosis, the square mosaic was present throughout the retina except in a centrodorsotemporal area where single, double and triple cones occurred randomly. Six cone visual pigments were found with maximum absorbance (λmax, in nm) in the short [S(431) and S(457)], middle [M(500), M(514) and M(527)], and long [L(550)] wavelengths, and a rod visual pigment with λmax at 491 nm. These pigments only partially matched the opsin repertoire detected by query of the Atlantic halibut genome. We conclude that the Atlantic halibut undergoes a complex re-organization of photoreceptors at metamorphosis resulting in a multi-mosaic retina adapted for a demersal life style.
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Project description:The Tokay gecko (Gekko gekko), a nocturnal lizard, has two kinds of visual pigments, P467 and P521. In spite of the pure-rod morphology of the photoreceptor cells, the biochemical properties of P521 and P467 resemble those of iodopsin (the chicken red-sensitive cone visual pigment) and rhodopsin, respectively. We have found that the amino acid sequence of P521 deduced from the cDNA was very similar to that of iodopsin. In addition, P467 has the highest homology with the chicken green-sensitive cone visual pigment, although it also has a relatively high homology with rhodopsins. These results give additional strength to the transmutation theory of Walls [Walls, G. L. (1934) Am. J. Ophthalmol. 17, 892-915], who proposed that the rod-shaped photoreceptor cells of lizards have been derived from ancestral cone-like photoreceptors. Apparently amino acid sequences of visual pigments are less changeable than the morphology of the photoreceptor cells in the course of evolution.
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Project description:Human color vision is mediated by the red, green, and blue cone visual pigments. Cone opsins are G-protein-coupled receptors consisting of an opsin apoprotein covalently linked to the 11-cis-retinal chromophore. All visual pigments share a common evolutionary origin, and red and green cone opsins exhibit a higher homology, whereas blue cone opsin shows more resemblance to the dim light receptor rhodopsin. Here we show that chromophore regeneration in photoactivated blue cone opsin exhibits intermediate transient conformations and a secondary retinoid binding event with slower binding kinetics. We also detected a fine-tuning of the conformational change in the photoactivated blue cone opsin binding site that alters the retinal isomer binding specificity. Furthermore, the molecular models of active and inactive blue cone opsins show specific molecular interactions in the retinal binding site that are not present in other opsins. These findings highlight the differential conformational versatility of human cone opsin pigments in the chromophore regeneration process, particularly compared to rhodopsin, and point to relevant functional, unexpected roles other than spectral tuning for the cone visual pigments.
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Project description:In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor 'transmutation'. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels.
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Project description:The role of the extracellular loop region of a short-wavelength sensitive pigment, Xenopus violet cone opsin, is investigated via computational modeling, mutagenesis, and spectroscopy. The computational models predict a complex H-bonding network that stabilizes and connects the EC2-EC3 loop and the N-terminus. Mutations that are predicted to disrupt the H-bonding network are shown to produce visual pigments that do not stably bind chromophore and exhibit properties of a misfolded protein. The potential role of a disulfide bond between two conserved Cys residues, Cys(105) in TM3 and Cys(182) in EC2, is necessary for proper folding and trafficking in VCOP. Lastly, certain residues in the EC2 loop are predicted to stabilize the formation of two antiparallel β-strands joined by a hairpin turn, which interact with the chromophore via H-bonding or van der Waals interactions. Mutations of conserved residues result in a decrease in the level of chromophore binding. These results demonstrate that the extracellular loops are crucial for the formation of this cone visual pigment. Moreover, there are significant differences in the structure and function of this region in VCOP compared to that in rhodopsin.
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