Evaluation of the role of the retinal G protein‐coupled receptor (RGR) in the vertebrate retina in vivo
Open accessAbstract
The retinal G protein-coupled receptor (RGR) is a protein that structurally resembles visual pigments and other G protein-coupled receptors. RGR may play a role as a photoisomerase in the production of 11-cis-retinal, the chromophore of the visual pigments. As the proposed function of RGR, in a complex with 11-cis-retinol dehydrogenase (RDH5), is to regenerate 11-cis-retinal under light conditions and RDH5 is expected to function in the light-independent part of the retinoid cycle, we speculated that the simultaneous loss of function of both proteins should more severely affect the rhodopsin regeneration capacity. Here, we evaluated the role of RGR using rgr-/- single and rdh5-/-rgr-/- double knockout mice under a number of light conditions. The most striking phenotype of rgr-/- mice after a single flash of light includes light-dependent formation of 9-cis- and 13-cis-retinoid isomers. These isomers are not formed in wild-type mice because either all-trans-retinal is bound to RGR and protected from isomerization to 9-cis- or 13-cis-retinal or because RGR is able to eliminate these isomers directly or indirectly. After intense bleaching, a transient accumulation of all-trans-retinyl esters and an attenuated recovery of 11-cis-retinal were observed. Finally, even under conditions of prolonged light illumination, as investigated in vitro in biochemical assays or in vivo by electroretinogram (ERG) measurements, no evidence of catalytic-like photoisomerization-driven production of 11-cis-retinal could be attained. These and previous results suggest that RGR and RDH5 are likely to function in the retinoid cycle, although their role is not essential and regeneration of visual pigment is only mildly affected by the absence of both proteins in rod-dominated mice.
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RGR, together with RPE65, contributes to the regeneration of 11-cis-retinal.
“Therefore, RGR, together with RPE65, contributes to the regeneration of 11-cis-retinal [55,56,57,58].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [58]
In the RPE, an additional source of 11-cis-retinal is a pathway with retinal G protein-coupled receptor (RGR) as the key enzyme; RGR preferentially binds all-trans-retinal, and within RGR a photon of light converts all-trans-retinal to 11-cis-retinal.
“In RPE, an additional source of 11-cis-retinal is also a pathway with retinal G protein-coupled receptor (RGR) as the key enzyme. RGR is a RHO homologue, which, contrary to RHO, preferentially binds all-trans-retinal. Within RGR, a photon of light converts all-trans-retinal to 11-cis-retinal, the chromophore of the visual pigments.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [58]
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- Authors
- Maeda, T., Van Hooser, J. P., Driessen, C. A. G. G., Filipek, S., Janssen, J. J. M., & Palczewski, K.
- Affiliations
- University of Washington (US)
- International Institute of Molecular and Cell Biology (PL)
- Radboud University Nijmegen (NL)
- Corresponding author
- Palczewski, Krzysztof
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2003-04-23
- Volume
- 85
- Issue
- 4
- Pages
- 944-956
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC1435694
- OpenAlex
- W2104293783
- Cited by
- 75
- References
- 7
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 1
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (EY13385, EY 09339, R01EY013385, R01EY009339)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- RDH5, 11-cis-retinal regeneration, retinoid cycle, photoisomerization, rhodopsin regeneration, retinol dehydrogenase, rod photoreceptors, knockout mice, electroretinogram
- MeSH terms
- Alcohol Oxidoreductases, Animals, Crosses, Genetic, Electroretinography, Eye Proteins, Photic Stimulation, Receptors, Cell Surface, Retina, Retinaldehyde, Retinoids, Mice, Knockout, Receptors, G-Protein-Coupled, Mice, In Vitro Techniques
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