title: The retinal G protein-coupled receptor (RGR) enhances isomerohydrolase activity independent of light.
abstract: Rod and cone visual pigments use 11-cis-retinal, a vitamin A derivative, as their chromophore. Light isomerizes 11-cis- into all-trans-retinal, triggering a conformational transition of the opsin molecule that initiates phototransduction. After bleaching all-trans-retinal leaves the opsin, and light sensitivity must be restored by regeneration of 11-cis-retinal. Under bright light conditions the retinal G protein-coupled receptor (RGR) was reported to support this regeneration by acting as a photoisomerase in a proposed photic visual cycle. We analyzed the contribution of RGR to rhodopsin regeneration under different light regimes and show that regeneration, during light exposure and in darkness, is slowed about 3-fold in Rgr(-/-) mice. These findings are not in line with the proposed function of RGR as a photoisomerase. Instead, RGR, independent of light, accelerates the conversion of retinyl esters to 11-cis-retinal by positively modulating isomerohydrolase activity, a key step in the "classical" visual cycle. Furthermore, we find that light accelerates rhodopsin regeneration, independent of RGR.
authors.affiliation: Laboratory for Retinal Cell Biology, University Hospital Zurich, Eye Clinic, Switzerland. awenzel@opht.unizh.ch
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Vitus
authors.initials: V
authors.lastname: Oberhauser
authors.forename: Edward N
authors.initials: EN
authors.lastname: Pugh
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lamb
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Marijana
authors.initials: M
authors.lastname: Samardzija
authors.forename: Edda
authors.initials: E
authors.lastname: Fahl
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Remé
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D005136:Eye Proteins / Q000032:analysis / Q000502:physiology; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010786:Photoreceptor Cells / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012038:Regeneration; D012160:Retina / Q000502:physiology*; D012172:Retinaldehyde / Q000737:chemistry*; D013237:Stereoisomerism; D019745:cis-trans-Isomerases / Q000378:metabolism*; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D043562:Receptors, G-Protein-Coupled; D012172:Retinaldehyde; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase