Opsins and melanopsins

Abstract

What are opsins? Opsins are generally considered members of the superfamily of G-protein coupled receptors. But not all opsins activate a G-protein. Their distinguishing features are a 7 transmembrane α-helical structure, and an ability to bind a vitamin A chromophore, retinaldehyde, using a lysine in the 7th α-helix. The range of amino acid identity among opsin families is 22–40%, and they have ∼17% identity to other hepta-helical receptor families.How do they work? Two well established functions are those of photosensor and photoisomerase (Figure 1Figure 1). In the photosensory opsins the chromophore, 11-cis-retinal, is located in a cage formed by the α-helices. Light is absorbed by 11-cis-retinal which is photoisomerised to all-trans. This conformational change allows the opsin to bind the α-subunit of the G-protein transducin. In the rods and cones of the retina G-protein activation leads to hyper-polarisation of the photoreceptor through cGMP-gated cation channels. The photoisomerase function is exhibited by retinal G-protein coupled receptor (RGR) opsin, expressed in the retinal pigment epithelium. It binds all-trans-retinal and uses light to convert it to the 11-cis configuration. Photoisomerisation is not thought to activate a G-protein but supplies the rod and cone opsins with 11-cis chromophore.Figure 1Vertebrate opsins are known to act as photosensors, where light induces a conformation change in the chromophore from the 11-cis-retinal to the all-trans configuration. This changes the opsin shape and results in the activation of a G-protein. Opsins that act as photoisomerases use light energy to convert all-trans-retinal into the 11-cis configuration, and supply photosensory opsins with chromophore.View Large Image | View Hi-Res Image | Download PowerPoint SlideHow many opsin families are there in vertebrates? On the basis of sequence similarity there are 14:7 are photosensory, including the 4 cone and 1 rod-opsin families, pineal-opsins, and vertebrate ancient (VA) opsins, first isolated from retinal horizontal and amacrine cells of teleost fish. Four other families, exorhodopsin, parapinopsin, tmt-opsin and encephalopsin, share relatively high levels of identity with the photosensory opsins (30–40%) but functional data are lacking. Other opsin families include RGR-opsin, melanopsin, and peropsin, a presumed photoisomerase.Why look for more photosensory and photoisomerase opsins? Photoreception is not limited to the rods and cones, but can occur in cells of the inner retina, pineal, brain or skin. Action spectra for these photoresponses have implicated opsin/vitamin A based photopigments, but the photosensory genes and proteins remain unknown. It is also unclear how photopigment chromophore is regenerated in photoreceptors that lack an retinal pigment epithelium-like structure. The assumption has been that there will be a ‘local’ photoisomerase to perform this task, but none has been identified.What is melanopsin and where is it expressed? Melanopsin was first isolated from the photo-sensitive melanophores of Xenopus. Orthologues have been found in most vertebrate classes, including mammals. All show little homology to the photosensory opsins and to each other. In mammals, melanopsin is expressed in a subset of photosensitive retinal ganglion cells, and in non-mammals, in photoreceptive structures such as the pineal and hypothalamus.Are melanopsins photosensors or photoisomerases? The expression of melanopsin in photoreceptors could indicate either a photosensory or photoisomerase function, but their homology to the known opsins predicts neither. If the melanopsins are novel photosensors then it will be critical to show that melanopsin not only binds retinal to form a photopigment with a sensitivity maxima predicted by action spectra, but that the melanopsin–chromophore complex can activate a phototransduction cascade. It is also possible that the melanopsins act as both photosensors and photoisomerases, and in this respect resemble the invertebrate photopigments.