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.
Kono
Masahiro
M
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. konom@musc.edu
Goletz
Patrice W
PW
Crouch
Rosalie K
RK
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