Opsin

Abstract: Here we report the identification of a novel human opsin, melanopsin, that is expressed in cells of the mammalian inner retina. The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22. This chromosomal localization and gene structure differs significantly from that of other human opsins that typically have four to seven exons. A survey of 26 anatomical sites indicates that, in humans, melanopsin is expressed only in the eye. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas. Notably, expression is not observed in retinal photoreceptor cells, the opsin-containing cells of the outer retina that initiate vision. The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.

Abstract: Organisms of all domains of life use photoreceptor proteins to sense and respond to light. The light-sensitivity of photoreceptor proteins arises from bound chromophores such as retinal in retinylidene proteins, bilin in biliproteins, and flavin in flavoproteins. Rhodopsins found in Eukaryotes, Bacteria, and Archaea consist of opsin apoproteins and a covalently linked retinal which is employed to absorb photons for energy conversion or the initiation of intra- or intercellular signaling.1 Both functions are important for organisms to survive and to adapt to the environment. While lower organisms utilize the family of microbial rhodopsins for both purposes, animals solely use a different family of rhodopsins, a specialized subset of G-protein-coupled receptors (GPCRs).1,2 Animal rhodopsins, for example, are employed in visual and nonvisual phototransduction, in the maintenance of the circadian clock and as photoisomerases.3,4 While sharing practically no sequence similarity, microbial and animal rhodopsins, also termed type-I and type-II rhodopsins, respectively, share a common architecture of seven transmembrane α-helices (TM) with the N- and C-terminus facing out- and inside of the cell, respectively (Figure ​(Figure11).1,5 Retinal is attached by a Schiff base linkage to the e-amino group of a lysine side chain in the middle of TM7 (Figures ​(Figures11 and ​and2).2). The retinal Schiff base (RSB) is protonated (RSBH+) in most cases, and changes in protonation state are integral to the signaling or transport activity of rhodopsins. Figure 1 Topology of the retinal proteins. (A) These membrane proteins contain seven α-helices (typically denoted helix A to G in microbial opsins and TM1 to 7 in the animal opsins) spanning the lipid bilayer. The N-terminus faces the outside of the cell ...

Abstract: We have identified an opsin, melanopsin, in photosensitive dermal melanophores of Xenopus laevis. Its deduced amino acid sequence shares greatest homology with cephalopod opsins. The predicted secondary structure of melanopsin indicates the presence of a long cytoplasmic tail with multiple putative phosphorylation sites, suggesting that this opsin’s function may be finely regulated. Melanopsin mRNA is expressed in hypothalamic sites thought to contain deep brain photoreceptors and in the iris, a structure known to be directly photosensitive in amphibians. Melanopsin message is also localized in retinal cells residing in the outermost lamina of the inner nuclear layer where horizontal cells are typically found. Its expression in retinal and nonretinal tissues suggests a role in vision and nonvisual photoreceptive tasks, such as photic control of skin pigmentation, pupillary aperture, and circadian and photoperiodic physiology.

Abstract: Mutation of RPE65 can cause severe blindness from birth or early childhood, and RPE65 protein is associated with retinal pigment epithelium (RPE) vitamin A metabolism. Here, we show that Rpe65-deficient mice exhibit changes in retinal physiology and biochemistry. Outer segment discs of rod photoreceptors in Rpe65-/- mice are disorganized compared with those of Rpe65+/+ and Rpe65+/- mice. Rod function, as measured by electroretinography, is abolished in Rpe65-/- mice, although cone function remains. Rpe65-/- mice lack rhodopsin, but not opsin apoprotein. Furthermore, all-trans-retinyl esters over-accumulate in the RPE of Rpe65-/- mice, whereas 11-cis-retinyl esters are absent. Disruption of the RPE-based metabolism of all-trans-retinyl esters to 11-cis-retinal thus appears to underlie the Rpe65-/- phenotype, although cone pigment regeneration may be dependent on a separate pathway.