Opsin

Opsins are a group of proteins made light-sensitive via the chromophore retinal (or a variant) found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in vision.
Opsin classification.
Opsins can be classified several ways, including function (vision, phototaxis, photoperiodism, etc.), type of chromophore (retinal, flavine, bilin), molecular structure (tertiary, quaternary), signal output (phosphorylation, reduction, oxidation), etc.
There are two groups of protein termed opsins. Type I opsins are employed by prokaryotes and by some algae (as a component of channelrhodopsins) and fungi, whereas animals use type II opsins. No opsins have been found outside these groups (for instance in plants, or placozoans).
At one time it was thought that type I and type II were related because of structural and functional similarities. With the advent of genetic sequencing it became apparent that sequence identity was no greater than could be accounted for by random chance. However, in recent years new methods have been developed specific to "deep phylogeny". As a result, several studies have found evidence of a possible phylogenetic relationship between the two. However, this does not necessarily mean that the last common ancestor of type I and II opsins was itself an opsin, a light sensitive receptor: all animal opsins arose (by gene duplication and divergence) late in the history of the large G-protein coupled receptor (GPCR) gene family, which itself arose after the divergence of plants, fungi, choanflagellates and sponges from the earliest animals. The retinal chromophore is found solely in the opsin branch of this large gene family, meaning its occurrence elsewhere represents convergent evolution, not homology. Microbial rhodopsins are, by sequence, very different from any of the GPCR families. According to one hypothesis, both type-I and type-II opsins belong to the "transporter-opsin-G protein-coupled receptor (TOG) superfamily", a proposed clade that includes G protein-coupled receptor (GPCR), Ion-translocating microbial rhodopsin (MR), and seven others.
Type I opsins.
Type I opsins (also known as microbial opsins) are seven-transmembrane-domain proteins. Most of them are ion channels or pumps instead of proper receptors and do not bind to a G protein. Type I opsins are found in all three domains of life: Archaea, Bacteria, and Eukaryota. In Eukaryota, type I opsins are found mainly in unicellular organisms such as green algae, and in fungi. In most complex multicellular eukaryotes, type I opsins have been replaced with other light-sensitive molecules such as cryptochrome and phytochrome in plants, and type II opsins in Metazoa (animals).
Microbial opsins are often known by the rhodopsin form of the molecule, i.e., rhodopsin (in the broad sense) = opsin + chromophore. Among the many kinds of microbial opsins are the proton pumps bacteriorhodopsin (BR) and xanthorhodopsin (xR), the chloride pump halorhodopsin (HR)
the photosensors sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII), as well as proteorhodopsin (PR), Neurospora opsin I (NOPI), Chlamydomonas sensory rhodopsins A (CSRA), Chlamydomonas sensory rhodopsins B (CSRB), channelrhodopsin (ChR), and archaerhodopsin (Arch).
Several type I opsins, such as proteo- and bacteriorhodopsin, are used by various bacterial groups to harvest energy from light to carry out metabolic processes using a non-chlorophyll-based pathway. Beside that, halorhodopsins of Halobacteria and channelrhodopsins of some algae, e.g. Volvox, serve them as light-gated ion channels, amongst others also for phototactic purposes. Sensory rhodopsins exist in Halobacteria that induce a phototactic response by interacting with transducer membrane-embedded proteins that have no relation to G proteins.
Type I opsins (like channelrhodopsin, halorhodopsin, and archaerhodopsin) are used in optogenetics to switch on or off neuronal activity. Type I opsins are preferred if the neuronal activity should be modulated at higher frequency, because they respond faster than type II opsins. This is because type I opsins are ion channels or proton/ion pumps and thus are activated by light directly, while type II opsins activate G-proteins, which then activate effector enzymes that produce metabolites to open ion channels.
Type II opsins.
Type II opsins (or animal opsins) are members of the seven-transmembrane-domain proteins (35–55 kDa) of the G protein-coupled receptor (GPCR) superfamily.
Type II opsins fall phylogenetically into four groups: C-opsins (Ciliary), Cnidops (cnidarian opsins), R-opsins (rhabdomeric), and Go/RGR opsins (also known as RGR/Go or Group 4 opsins). The Go/RGR opsins are divided into four sub-clades: Go-opsins, RGR, Peropsins, and Neuropsins. C-opsins, R-opsins, and the Go/RGR opsins are found only in Bilateria.
Type II visual opsins are traditionally classified as either ciliary or rhabdomeric. Ciliary opsins, found in vertebrates and cnidarians, attach to ciliary structures such as rods and cones. Rhabdomeric opsins are attached to light-gathering organelles called rhabdomeres. This classification cuts across phylogenetic categories (clades) so that both the terms "ciliary" and "rhabdomeric" can be ambiguous. Here, "C-opsins (ciliary)" refers to a clade found exclusively in Bilateria and excludes cnidarian ciliary opsins such as those found in the box jellyfish. Similarly, "R-opsin (rhabdomeric)" includes melanopsin even though it does not occur on rhabdomeres in vertebrates.
C-opsins (ciliary).
Ciliary opsins (or c-opsins) are expressed in ciliary photoreceptor cells, and include the vertebrate visual opsins and encephalopsins. They convert light signals to nerve impulses via cyclic nucleotide gated ion channels, which work by increasing the charge differential across the cell membrane (i.e. hyperpolarization.)
Vertebrate visual opsins.
Vertebrate visual opsins are a subset of C-opsins (ciliary). They are expressed in the vertebrate retina and mediate vision. They can be further subdivided into rod opsins and four types of cone opsin. Rod opsins (rhodopsins, usually denoted Rh), are used in dim-light vision, are thermally stable, and are found in the rod photoreceptor cells. Cone opsins, employed in color vision, are less-stable opsins located in the cone photoreceptor cells. Cone opsins are further subdivided according to their absorption maxima ("λ"max), the wavelength at which the highest light absorption is observed. Evolutionary relationships, deduced using the amino acid sequence of the opsins, are also frequently used to categorize cone opsins into their respective group. Both methods predict four general cone opsin groups in addition to rhodopsin.
Vertebrates typically have four cone opsins (LWS, SWS1, SWS2, and Rh2) inherited from the first vertebrate (and thus predating the first vertebrate), as well as the rod opsin, rhodopsin (Rh1), which emerged after the first vertebrate but before the first Gnathostome (jawed vertebrate). These five opsins emerged through a series of gene duplications beginning with LWS and ending with Rh1. Each one has since evolved into numerous variants and thus constitutes an opsin family or subtype.
Humans have the following set of photoreceptor proteins responsible for vision:
Pinopsins.
The first Pineal Opsin (Pinopsin) was found in the chicken pineal gland. It is a blue sensitive opsin ("λ"max = 470 nm).
wide range of expression in the brain, most notably in the pineal region
Vertebrate Ancient (VA) opsin.
Vertebrate Ancient (VA) opsin has three isoforms VA short (VAS), VA medium (VAM), and VA long (VAL). It is expressed in the inner retina, within the horizontal and amacrine cells, as well as the pineal organ and habenular region of the brain. It is sensitive to approximately 500 nm [14], found in most vertebrate classes, but not in mammals.
Parapinopsins.
The first parapinopsin (PP) opsin was found in the parapineal organ of the catfish. The parapinopsin of lamprey is a UV-sensitive opsin ("λ"max = 370 nm). The teleosts have two groups of parapinopsins, one is sensitive to UV ("λ"max = 360-370 nm), the other is sensitive to blue ("λ"max = 460-480 nm) light.
Parietopsins.
The first parietopsin was found in the photoreceptor cells of the lizard parietal eye. The lizard parietopsin is green-sensitive ("λ"max = 522 nm), and despite it is a c-opsin, like the vertebrate visual opsins, it does not induce hyperpolarization via a Gt-protein, but induces depolarization via a Go-protein.
OPN3 (Encephalopsin or Panopsin).
Panopsins are found in many tissues (skin, brain, testes, heart, liver, kidney, skeletal muscle, lung, pancreas and retina). They were originally found in the human and mouse brain and thus called encephalopsin.
The first invertebrate panopsin was found in the ciliary photoreceptor cells of the annelid "Platynereis dumerilii" and is called c(iliary)-opsin. This c-opsin is UV-sensitive ("λ"max = 383 nm) and can be tuned by 125 nm at a single amino-acid (range "λ"max = 377 - 502 nm). Thus, not unsurprisingly, a second but cyan sensitive c-opsin ("λ"max = 490 nm) exists in "Platynereis dumerilii". The first c-opsin mediates in the larva UV induced gravitaxis. The gravitaxis forms with phototaxis a ratio-chromatic depth-gauge. In different depths, the light in water is composed of different wavelengths: First the red (> 600 nm) and the UV and violet (< 420 nm) wavelengths disappear. The higher the depth the narrower the spectrum so that only cyan light (480 nm) is left. Thus, the larvae can determine their depth by color. The color unlike brightness stays almost constant independent of time of day or the weather, for instance if it is cloudy.
Panopsins are also expressed in the brains of some insects. The panopsins of mosquito and pufferfish absorb maximally at 500 nm and 460 nm, respectively. Both activate in vitro Gi and Go proteins.
The panopsins of teleost fish are called: Teleost multiple tissue (TMT) opsins.
Teleost Multiple Tissue (TMT) Opsin.
Teleost fish opsins are expressed in many tissues and therefore called Teleost Multiple Tissue (TMT) opsins. TMT opsins form three groups which are most closely related to a fourth groups the panopsins. In fact, TMT opsins in teleost fish are orthologous to the panopsins in the other vertebrates. They also have the same introns and the same place, which confirms that they belong together.
Cnidarian opsins.
Cnidaria, which include jellyfish, corals, and sea anemones, are the most basal animals to possess complex eyes. Jellyfish opsins in the rhopalia couple to Gs-proteins raising the intracellular cAMP level. Coral opsins can couple to Gq-proteins and Gc-proteins. Gc-proteins are a subtype of G-proteins specific to cnidarians. The cnidarian opsins have been identified as one group and so called cnidops, however at least some of them belong to the c-opsins, r-opsins, and Go/RGR-opsins found in bilaterians.
r-opsins (rhabdomeric) / Gq-coupled.
Rhabdomeric opsins (or r-opsins) are also known as Gq-opsins, because they couple to a Gq-protein. R-opsins are used by molluscs and arthropods. Arthropods appear to attain colour vision in a similar fashion to the vertebrates, by using three (or more) distinct groups of opsins, distinct both in terms of phylogeny and spectral sensitivity. The r-opsin melanopsin is also expressed in vertebrates, where it regulates circadian rhythms and mediates the pupillary reflex.
Unlike c-opsins, r-opsins are associated with canonical transient receptor potential ion channels; these lead to the electric potential difference across a cell membrane being eradicated (i.e. depolarization).
The identification of the crystal structure of squid rhodopsin is likely to further our understanding of its function in this group.
Arthropods use different opsins in their different eye types, but at least in "Limulus" the opsins expressed in the lateral and the compound eyes are 99% identical and presumably diverged recently.
Melanopsin OPN4.
Involved in circadian rhythms, pupillary reflex, and color correction in high-brightness situations. Phylogenetically a member of the R-opsin (rhabdomeric) group, functionally and structurally an r-opsin, but does not occur in rhabdomeres.
Go/RGR (Group 4) opsins.
Go/RGR opsins include Go-opsins, RGR-opsins, neuropsins, and peropsins.
Go-opsins.
Go-opsins are absent from higher vertebrates and ecdysozoans. They are found in the ciliary photoreceptor cells of the scallop eye and the basal chordate amphioxus. In "Platynereis dumerilii" however, a Go-opsin is expressed in the rhabdomeric photoreceptor cells of the eyes.
RGR opsins.
RGR opsins, also known as Retinal G protein coupled receptors are expressed in the retinal pigment epithelium (RPE) and Müller cells. They preferentially bind all-trans-retinal in the dark instead of 11-cis-retinal. RGR opsins were thought to be photomerases but instead, they regulate retinoid traffic and production. In particular, they speed up light-independently the production of 11-cis-retinol (a precursor of 11-cis-retinal) from all-trans-retinyl-esters. However, the all-trans-retinyl-esters are made available light-dependently by RGR-opsins. Whether RGR-opsins regulate this via a G-protein or another signaling mechanism is unknown. The cattle RGR opsin absorbs maximally at different wavelengths depending on the pH-value. At high pH it absorbs maximally blue (469 nm) light and at low pH it absorbs maximally UV (370 nm) light.
Peropsin.
Peropsin, a visual pigment-like receptor, is a protein that in humans is encoded by the "RRH" gene.
Neuropsins.
Neuropsins are sensitive to UVA, typically at 380 nm. They are found in the brain, testes, skin, and retina of humans and rodents, as well as in the brain and retina of birds. In birds and rodents they mediate ultraviolet vision. They couple to Gi-proteins. In humans, Neuropsin is encoded by the OPN5 gene. In the human retina, its function is unknown. In the mouse, it photo-entrains the retina and cornea at least ex vivo.
Unclassified.
Extraretinal (or extra-ocular) Rhodopsin-Like Opsins (Exo-Rh).
These pineal opsins, found in the Actinopterygii (ray-finned fish) apparently arose as a result of gene duplication from Rh1 (rhodopsin). These opsins appear to serve functions similar to those of pinopsin found in birds and reptiles.
Structure and function.
Opsin proteins covalently bind to a vitamin A-based retinaldehyde chromophore through a Schiff base linkage to a lysine residue in the seventh transmembrane alpha helix. In vertebrates, the chromophore is either 11-"cis"-retinal (A1) or 11-"cis"-3,4-didehydroretinal (A2) and is found in the retinal binding pocket of the opsin. The absorption of a photon of light results in the photoisomerization of the chromophore from the 11-"cis" to an all-"trans" conformation. The photoisomerization induces a conformational change in the opsin protein, causing the activation of the phototransduction cascade. The opsin remains insensitive to light in the "trans" form. It is regenerated by the replacement of the all-"trans" retinal by a newly synthesized 11-"cis"-retinal provided from the retinal epithelial cells. Opsins are functional while bound to either chromophore, with A2-bound opsin "λ"max being at a longer wavelength than A1-bound opsin.
Opsins contain seven transmembrane α-helical domains connected by three extra-cellular and three cytoplasmic loops. Many amino acid residues, termed "functionally conserved residues", are highly conserved between all opsin groups, indicative of important functional roles. All residue positions discussed henceforth are relative to the 348 amino acid bovine rhodopsin crystallized by Palczewski "et al." Lys296 is conserved in all known opsins and serves as the site for the Schiff base linkage with the chromophore. Cys138 and Cys110 form a highly conserved disulfide bridge. Glu113 serves as the counterion, stabilizing the protonation of the Schiff linkage between Lys296 and the chromophore. The Glu134-Arg135-Tyr136 is another highly conserved motif, involved in the propagation of the transduction signal once a photon has been absorbed.
Certain amino acid residues, termed "spectral tuning sites", have a strong effect on "λ"max values. Using site-directed mutagenesis, it is possible to selectively mutate these residues and investigate the resulting changes in light absorption properties of the opsin. It is important to differentiate "spectral tuning sites", residues that affect the wavelength at which the opsin absorbs light, from "functionally conserved sites", residues important for the proper functioning of the opsin. They are not mutually exclusive, but, for practical reasons, it is easier to investigate spectral tuning sites that do not affect opsin functionality. For a comprehensive review of spectral tuning sites see Yokoyama and Deeb. The impact of spectral tuning sites on "λ"max differs between different opsin groups and between opsin groups of different species.
Opsins in the human eye, brain, and skin.
RPE, retinal pigment epithelium; ipRGC, intrinsically photosensitive retinal ganglion cells; OPL, outer plexiform layer; IPL, inner plexiform layer; GCL, ganglion cell layer