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PMID: 12716426 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Evaluation of the role of the retinal G protein-coupled receptor (RGR) in the vertebrate retina in vivo.

Journal of neurochemistry ·Vol. 85 ·No. 4 ·2003-05-00 ·Pages 944-56

Maeda T, Van Hooser JP, Driessen CA, Filipek S, Janssen JJ, Palczewski K

Abstract

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.

MeSH Terms
Alcohol Oxidoreductases/genetics,metabolism Animals Crosses, Genetic Electroretinography Eye Proteins/chemistry,genetics,metabolism In Vitro Techniques Mice Mice, Knockout Photic Stimulation/methods Receptors, Cell Surface/chemistry,genetics,metabolism Receptors, G-Protein-Coupled Retina/chemistry,metabolism Retinaldehyde/metabolism Retinoids/chemistry,metabolism
Chemicals
Eye Proteins G protein-coupled receptor RGR Receptors, Cell Surface Receptors, G-Protein-Coupled Retinoids Alcohol Oxidoreductases retinol dehydrogenase Retinaldehyde
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Maeda Tadao
Department of Ophthalmology, University of Washington, Seattle, WA 98195-6485, USA.
Van Hooser J Preston
Driessen Carola A G G
Filipek Sławomir
Janssen Jacques J M
Palczewski Krzysztof
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Article Info
Journal
Journal of neurochemistry
Abbr.
J Neurochem
ISSN
0022-3042
DOI
10.1046/j.1471-4159.2003.01741.x
Published
2003-05-00
Pages
944-56
Language
English
Region
England
NLM ID
2985190R
PMCID
PMC1435694
Subset
IM
Grants
NEI NIH HHS · R01 EY009339 · United States
NEI NIH HHS · R01 EY013385 · United States
NEI NIH HHS · EY 09339 · United States
NEI NIH HHS · EY 13385 · United States
External Links
PubMed source DOI: 10.1046/j.1471-4159.2003.01741.x PMC Full Text View journal details
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