11-cis- and all-trans-retinols can activate rod opsin: rational design of the visual cycle.
Rhodopsin is the photosensitive pigment in the rod photoreceptor cell. Upon absorption of a photon, the covalently bound 11- cis-retinal isomerizes to the all- trans form, enabling rhodopsin to activate transducin, its G protein. All -trans-retinal is then released from the protein and reduced to all -trans-retinol. It is subsequently transported to the retinal pigment epithelium where it is converted to 11- cis-retinol and oxidized to 11- cis-retinal before it is transported back to the photoreceptor to regenerate rhodopsin and complete the visual cycle. In this study, we have measured the effects of all -trans- and 11- cis-retinals and -retinols on the opsin's ability to activate transducin to ascertain their potentials for activating the signaling cascade. Only 11- cis-retinal acts as an inverse agonist to the opsin. All -trans-retinal, all -trans-retinol, and 11- cis-retinol are all agonists with all -trans-retinal being the most potent agonist and all -trans-retinol being the least potent. Taken as a whole, our study is consistent with the hypothesis that the steps in the visual cycle are optimized such that the rod can serve as a highly sensitive dim light receptor. All -trans-retinal is immediately reduced in the photoreceptor to prevent back reactions and to weaken its effectiveness as an agonist before it is transported out of the cell; oxidation of 11- cis-retinol occurs in the retinal pigment epithelium and not the rod photoreceptor cell because 11- cis-retinol can act as an agonist and activate the signaling cascade if it were to bind an opsin, effectively adapting the cell to light.
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. konom@musc.edu
Masahiro
M
Kono
Patrice W
PW
Goletz
Rosalie K
RK
Crouch
D000818:Animals; D019556:COS Cells; D002417:Cattle; D002522:Chlorocebus aethiops; D000882:Haplorhini; D010786:Photoreceptor Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012172:Retinaldehyde / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012243:Rhodopsin / Q000378:metabolism*; D015293:Transducin / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*; D014801:Vitamin A / Q000737:chemistry / Q000494:pharmacology*
D014801:Vitamin A; D012243:Rhodopsin; D015293:Transducin; D012172:Retinaldehyde