The retinal G protein-coupled receptor (RGR) enhances isomerohydrolase activity independent of light.
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.
Wenzel
Andreas
A
Laboratory for Retinal Cell Biology, University Hospital Zurich, Eye Clinic, Switzerland. awenzel@opht.unizh.ch
Oberhauser
Vitus
V
Pugh
Edward N
EN
Lamb
Trevor D
TD
Grimm
Christian
C
Samardzija
Marijana
M
Fahl
Edda
E
Seeliger
Mathias W
MW
Remé
Charlotte E
CE
von Lintig
Johannes
J
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
D002352:Carrier Proteins; D005136:Eye Proteins; D043562:Receptors, G-Protein-Coupled; D012172:Retinaldehyde; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase