Focus Article

Evolution and diversity of opsins

Akihisa Terakita, Emi Kawano-Yamashita and Mitsumasa Koyanagi
Many animals capture light information via opsin-based pigments. Several thousands of opsins have been identied thus far and the opsin family is divided into eight groups. Members belonging to four out of the eight groups have been elucidated to couple to transducin, Go, Gs, and Gq, respectively, in photoreceptor cells. Accumulated evidence suggests a novel classication of the animal phototransductions, cyclic nucleotide signaling mediated by transducin, Go or Gs in ciliary photoreceptor cells and phosphoinositol signaling mediated by Gq in rhabdomeric photoreceptor cells. Varied opsin-based pigments are spectroscopically classied into two types, bleaching and bistable pigments; that is, the photoproduct of vertebrate visual pigments dissociates its chromophore retinal over time and bleaches, whereas most other opsin-based pigments convert to a stable photoproduct, which can revert to original dark state by subsequent light absorption. Mutational analyses of the both types of pigments implied that during molecular evolution of the vertebrae visual pigments, displacement of the counterion, important amino acid residue for visible light absorption of opsin-based pigment, resulted in not only unique bleaching property but also acquisition of red-sensitive visual pigment and higher G-protein activation ability generated by larger light-induced conformational change of the pigment. Interestingly, a bleaching pigment rhodopsin and parapinopsin, which closely relates to the vertebrate visual pigment but has a bistable nature, couple to visual arrestin and arrestin, respectively, in the lamprey pineal organ, suggesting the bleaching property also might facilitate the evolution of visual arrestin which is specialized for vertebrate visual function. 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
How to cite this article:

WIREs Membr Transp Signal 2012, 1:104111. doi: 10.1002/wmts.6

INTRODUCTION

ost animals capture light information by opsinbased photosensitive pigments for vision and nonvisual function. The opsin pigment is a typical G-protein-coupled receptor (GPCR) and consists of a protein moiety, opsin and a retinal chromophore.1,2 More than 2000 kinds of opsins have been identied and many animals possess various kinds of opsin genes. Because opsin-based pigments function at the entrance of photoreceptor cells, it can be speculated that molecular properties and functional properties of opsin-based pigments are responsible largely for functional characteristics of the photoreceptor cells. Thus, it is expected that evolution and diversity of opsin could tell us what happened during evolution of molecular basis of vision. Here we discuss on
to: terakita@sci.osaka-cu.ac.jp Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Osaka, Japan
Correspondence

molecular evolution and diversity of opsin as well as related signal transduction cascades.

THE DIVERSITY OF OPSINS AND THE CLASSIFICATION OF PHOTOTRANSDUCTION CASCADES

More than 2000 kinds of opsins identied so far are classied into at least eight groups based on amino acid sequence similarity: seven groups of bilaterian opsins (Gt-coupled opsin, encephalopsin/TMT-opsin, Gq-coupled opsin, Go-coupled opsin, neuropsin, peropsin, and photoisomerase groups) and one cnidarian opsin group (Gs-coupled opsin group)3 (Figure 1). A light signal captured by opsin pigments is transmitted to sequential biochemical reactions composed of a G protein, an effector enzyme and an ion channel, and leads to electrophysiological cellular responses. G-protein-mediated phototransduction
Vo lu me 1, Jan u ary/Febru ary 2012

104

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

WIREs Membrane Transport and Signaling

Evolution and diversity of opsins

(a)

Cyclic nucleotide / ciliary photoreceptor

Gs
Hydra opsin
Sea anemone opsin Box jellyfish opsin Human encephalopsin (Fish TMT-opsin) Rag-worm c-opsin Amphioxus rhodopsin Human rhodopsin Human blue Human red Fruit fly Rh1 Lamprey parapinopsin squid rhodopsin Amphioxus peropsin Amphioxus melanopsin

Disk

Cilium Nucleus

Go

Scallop Go-rhodopsin

Rhabdomere

Microvillus

Human neuropsin

Gt

Nucleus

Human melanopsin

Human peropsin

Gq
Human rgr

Phosphoinositol / rhabdomeric photoreceptor

(b)

Squid retinochrome

Photoisomerase

Phototransduction cascade Ciliary photoreceptor Gt -coupled opsin Go -coupled opsin Gs -coupled opsin Gt Go Gs PDE GC AC cGMP cGMP cAMP CNG channel CNG channel CNG channel

Gq -coupled opsin

Rhabdomeric photoreceptor PIP2 Gq PLC TRP/TRPL channel DAG/IP3

(c)

Bleaching pigment (eg. Vertebrate visual pigment)

Bistable pigment (eg. Invertebrate visual pigment)

Reversible

Dark

Photoproduct

Dark

Photoproduct

Opsin

FIGURE 1 | The diversity of opsin-based pigments. (a) The molecular phylogenetic tree of opsins. The thousands of opsins identied thus far are divided into eight groups. (b) G-protein-mediated phototransduction cascades driven by varied opsin-based pigments. (c) Photoreaction of typical opsin-based pigments. Opsin-based pigments are divided into two groups based on the molecular properties of their photoproducts, bleaching pigments and bistable pigments.

Vo lu me 1, Jan u ary/Febru ary 2012

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

105

Focus Article

wires.wiley.com/mts

cascade has been elucidated for the pigments belonging to four out of the eight groups.2,4 Recently, we discovered functional and evolutionary relationships between phototransduction cascades and photoreceptor cell types, which were distinguished based on morphological characteristics of the photoreceptive portion of the photoreceptor cells, namely the ciliary and rhabdomeric photoreceptor cells.3 Vertebrate visual pigments, which are Gt-coupled opsin-based pigments, are found in rods and cones and activate transducin (Gt), which in turn activates phosphodiesterase, which hydrolyzes cGMP to 5 GMP. A decrease in cGMP concentration in the photoreceptor cells results in closure of the cyclic nucleotide (cGMP)-gated cation (CNG) channel and leads to a hyperpolarizing response of the cells4 (Figure 1). Gocoupled opsins have been found in scallop ciliary-type photoreceptor cells and amphioxus.5,6 In the scallop ciliary cells, the Go-coupled opsin-based pigment activates Go and subsequently elevates cGMP levels in the photoreceptor cells to open the CNG channel.5,7 In the ciliary-type visual cells of the cnidarian box jellysh, one of the most primitive animals that have developed eyes, Gs-coupled opsin-based pigment activates Gs, which in turn activates adenylyl cyclase and elevates cAMP levels.3 On the other hand, Gq-coupled opsin-based pigments drive phosphatidylinositol-related cascades, not cyclic nucleotides.8 In molluscan and arthropod visual cells, which are typical rhabdomeric photoreceptor cells with microvilli, Gq-coupled opsin-based pigments activate Gq, which in turn stimulates phospholipase C to hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DG) and inositol 1,4,5triphosphate (IP3) to initiate the phosphoinositol cascade. This cascade leads to a depolarizing response of the photoreceptor cells.4 In Drosophila, depletion of PIP2 underlies opening the transient receptor potential (TRP)/transient receptor potential-like (TRPL) channels to generate a depolarizing response.9 On the other hand, a DG-related unsaturated fatty acid can also open the channels.10 Interestingly, melanopsin, an opsin gene orthologous to invertebrate Gq-coupled visual pigments, has spectroscopic characteristics almost identical to those of invertebrate Gq-coupled opsin-based pigments and drives the Gqmediated phototransduction cascade.1116 Melanopsin localizes to rhabdomeric photoreceptor cells in amphioxus17 and mammalian intrinsically photosensitive retinal ganglion cells,1821 which are thought to have shared a common ancestral type with modern-day rhabdomeric photoreceptor cells.22 As mentioned, cnidarian, molluscan, and vertebrate ciliary photoreceptor cells contain different
106

sets of opsin-based pigments, G-proteins, and effector enzymes, but they employ the same type of second messenger, a cyclic nucleotide (cAMP and cGMP), and utilize the CNG channel. Furthermore, protostome and deuterostome rhabdomeric photoreceptors, including vertebrate photoreceptive retinal ganglion cells, share orthologous opsins and nearly identical Gq-mediated phototransduction cascades. These ndings clearly support the hypothesis of photoreceptor classications; that is, animals possess two morphologically distinct photoreceptor cell types, ciliary-type cells and rhabdomeric-type cells.23 We therefore proposed a novel classication of animal phototransduction and photoreceptor cells, including the previous evolutionary implications on relationship between opsin-based pigments and photoreceptor cells.17,23,24 The rhabdomeric photoreceptor cell uses phosphoinositol signaling mediated by Gq, and the ciliary photoreceptor cell contains cyclic nucleotide signaling mediated by Gt, Go, or Gs3 (Figure 1).

THE EVOLUTION OF VERTEBRATE VISUAL PIGMENTS Pigment Properties

Several lines of experimental evidence obtained through the use of native and recombinant opsinbased pigments have revealed that the Gq-coupled opsin, Go-coupled opsin, peropsin, and neuropsin groups contain a bistable pigment that has two stable states, a dark state and a photoproduct that reverts to the original dark state by subsequent light absorption (Figure 1(c)).2,8,25,26 A vertebrate nonvisual pigment, parapinopsin, shows bistable characteristics, although the pigment is classied into the Gt-coupled opsin group, which contains vertebrate visual pigments with bleaching property (the photoproduct of vertebrate visual pigments releases its retinal chromophore and bleaches; Figure 1(c)).27,28 A cnidarian opsin-based pigment (the jellysh pigment) is converted to a stable photoproduct that does not revert to its original dark state by subsequent light irradiation, unlike typical bistable pigments.3 These photoproduct properties imply that bleaching pigments evolved from a nonbleaching opsin-based pigment, possibly a bistable pigment, although it is unclear whether the members of the encephalopsin/TMT-opsin group are bistable in nature.

Acquisition of Glu113 Counterion

In opsin-based pigment sensitive to visible light, a retinal chromophore binds to lysine residue at position 296 (bovine rhodopsin numbering system) via
Vo lu me 1, Jan u ary/Febru ary 2012

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

WIREs Membrane Transport and Signaling

Evolution and diversity of opsins

Ancestral opsin pigment (Glu181) C

Invertebrate visual pigment (Glu181) C

Evolution of molecular basis of vertebrate vision

N C C Higher G protein activation efficiency by larger conformational change N Counterion displacement from Glu181 to Glu113 Mutation of Glu181 to His181 N C Red-sensitive cone visual pigment N

Acquisition of Glu113 (Glu181)

FIGURE 2 | Counterion displacement during the molecular evolution of vertebrate visual pigments. Opsin binds to a retinal chromophore via a
protonated Schiff base. The proton on the Schiff base is unstable, and the counterion, a negatively charged amino acid residue stabilizes the proton. Counterion displacement occurred during molecular evolution, and both the new (Glu113) and former (Glu181) counterions might facilitate the acquisition of new molecular properties of opsin-based pigments.

protonated Schiff base.2931 A counterion, negatively charged amino acid residue, stabilizes the protonated Schiff base and is essential for visible light absorption by opsin-based pigments (Figure 2). Mutational analyses using varied opsin-based pigments have revealed that the position of the counterion is different between bleaching and bistable pigments. Vertebrate visual pigments with bleaching properties have a glutamic acid residue as a counterion at position 113 (Glu113) in the third helix (note that the carboxylate of Glu113 stabilizes the protonated Schiff base).3234 However, in most bistable pigments, Glu181 in the connecting loop between the fourth and fth helices acts as the counterion.27,35 Interestingly, parapinopsin, which is close to vertebrate bleaching visual pigments, exhibits a bistable nature and possesses a Glu181 counterion.27,28 The difference in counterion position suggests that counterion displacement from Glu181 to Glu113 occurred during the molecular evolution of vertebrate visual pigments and promoted acquisition of the bleaching property. Counterion displacement resulted in two important amino acid residues, the new counterion Glu113 and the former counterion Glu181, each of which could potentially mediate the acquisition of new functional properties of vertebrate visual pigments as described below. In vertebrate red-sensitive cone visual pigments, the amino acid residue at position 181 is occupied by histidine. His181 is an essential amino acid residue for chloride ion binding and thus the red-sensitivity of the pigment; it forms a chloride-binding site with
Vo lu me 1, Jan u ary/Febru ary 2012

other residues, and binding of chloride is responsible for the red shift of the absorption spectrum. Thus, the mutation of Glu181 to His181, after acquisition of the new counterion Glu113 and decrease of importance of Glu181 as the counterion to allow its mutation, may have promoted the acquisition of red-sensitive cone visual pigment.27 As mentioned above, a different counterion position may be related to the bistable or bleaching property of the photoproduct. In contrast to Glu181, accumulating evidence indicates that the Glu113 counterion serves as an intramolecular switch to form the photoproduct that activates the G protein; that is, Glu113 acts as a counterion to stabilize a proton on the Schiff base in the dark state and also serves as a proton acceptor on the Schiff base in the photoproduct. This proton transfer, unique to bleaching pigments (vertebrate visual pigments), results in a photoproduct with an unprotonated retinal Schiff base. Interestingly, G-protein activation efciency of the bistable pigments Go -coupled opsin pigment and parapinopsin is lower than that of bovine rhodopsin by approximately 50- and 20fold, respectively.27 A recent site-specic uorescence study suggested that the conformational change of the protein moiety of parapinopsin upon photoactivation is smaller than that of bovine rhodopsin.36 These studies strongly suggest that the newer counterion, Glu113, could provide a larger conformational change in opsin pigments and a higher G-protein activation efciency, which could contribute to achieve
107

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

Focus Article

wires.wiley.com/mts

a highly photosensitive visual system. In invertebrate visual cells and mammalian intrinsic photosensitive retinal ganglion cells, a photon captured by bistable pigments, Gq-coupled visual pigment and melanopsin, respectively, is also efciently transduced to cellular light response.37 Downstream of G-protein signaling rather than the pigment/G-protein step might contribute the high light-signaling efciency in such bistable pigment-photoreceptor cells.38 The difference in the amplitude of the lightinduced conformational change may also be related to the difference in photoreversibility between the two opsin-based pigments. The large conformational change observed in bovine rhodopsin might enable so much internal rearrangement within the protein that it cannot be converted back to a dark state structure by further light-induced photoisomerization of the retinal. Therefore, it is tempting to speculate that, during the molecular evolution of vertebrate visual pigments, the pigments acquired higher G-protein activation ability through the acquisition of larger conformational changes, with the abolishment of photoreversibility and the bistable nature of the pigments as a by-product.36

Rod opsin Bleach Cone opsin

Visual arrestin

Rod arrestin Cone arrestin

Parapinopsin Non-bleach (bistable)

b-Arrestin

Ci-opsin 1 (ascidian)

Ci-Arrestin (ascidian)

FIGURE 3 | A schematic presentation of the correlation between the

molecular evolution of photopigments and arrestins. The right and left trees show the phylogenetic relationships of chordate photopigments and arrestins, respectively. The domain architectures of arrestins in the left tree show three types of arrestins that have a clathrin-binding domain (the lled circle). The arrows that connect the trees indicate the biochemical interactions between photopigments and arrestins. Note that pigment property of Ci-opsin1 has not been reported.

THE EVOLUTIONARY RELATIONSHIP BETWEEN OPSINS AND OTHER PHOTOTRANSDUCTION MOLECULES

The acquisition of the Glu113 counterion might have promoted the acquisition of bleaching properties, including larger conformational changes. To understand the molecular evolution of vision, it is important to elucidate the effect that the emergence of the bleaching pigment had on the evolution of phototransduction proteins. In vertebrate visual cells, the light-absorbed visual pigment binds to signal transduction proteins specialized for light-sensing, such as visual G-protein transducin and visual arrestin, which binds to the light-stimulated visual pigment to inhibit G-protein-mediated signaling.4 Ascidians, some of the invertebrates most closely related to vertebrates, have an opsin-based pigment Ci-opsin1, which is related to vertebrate visual and nonvisual pigments (Figure 3), but a transducin or a visual arrestin gene has not been found in the genomes of ascidians. Interestingly, Ciopsin1 colocalizes with a -arrestin-like arrestin, the molecular properties of which are similar to those of the vertebrate nonvisual arrestin, -arrestin.39 On the basis of these facts, we can predict that the evolution of vertebrate visual opsins may have been correlated with or promoted the evolution of signaling proteins that bind to vertebrate visual pigments.
108

To test this hypothesis, we compared proteins that bind to parapinopsin with those that bind to rhodopsin because parapinopsin is a bistable pigment that most closely resembles vertebrate visual pigments with bleaching property.40 We investigated the lamprey pineal organ, in which parapinopsin- and rhodopsin-containing cells are located in the dorsal and ventral regions, respectively.28,41 The spatial separation of the pigments allowed us to easily compare the parapinopsin and rhodopsin systems in the same organ. The results of immunohistochemical studies using antibodies against visual arrestin and transducin indicate that transducin or transducin-like G proteins localize to both parapinopsin-containing and rhodopsin-containing photoreceptor cells, whereas visual arrestin localizes only to rhodopsin-containing cells. Therefore, we investigated what kind of arrestin binds to parapinopsin. We found that -arrestin, which binds to stimulated GPCRs other than opsin-based pigments,4246 localizes to parapinopsin-containing cells, in contrast to the localization of visual arrestin in rhodopsincontaining cells.40 In general, mammalian -arrestin is implicated not only in the termination of GPCR signaling but also in clathrin-mediated GPCR internalization, which produces granules or vesicles that contain both -arrestin and internalized GPCRs.42,45 Therefore, we investigated the behavior and function of -arrestin using cultured cells that express parapinopsin and -arrestin as well as cells from the lamprey pineal organ.40 The experimental data suggested that -arrestin binds to parapinopsin in a light-dependent manner, similar to the binding of visual arrestin to visual pigments. Interestingly, the -arrestin-mediated clathrin-related internalization of parapinopsin has also been suggested in both
Vo lu me 1, Jan u ary/Febru ary 2012

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

WIREs Membrane Transport and Signaling

Evolution and diversity of opsins

cultured cells and parapinopsin-containing photoreceptor cells of the pineal organ, unlike visual arrestin. In parapinopsin-containing photoreceptor cells, the vesicles or granules formed by internalization contain parapinopsin and -arrestin but not G proteins. Therefore, -arrestin-mediated internalization may underlie the selective and complete removal of the stable photoproduct from the signal transduction locus, the outer segments of the photoreceptor cells. The physiological and evolutionary relevance of different kinds of arrestins and pigment properties is interesting. The photoproduct of the visual pigment rhodopsin bleaches over time due to the release of the all-trans retinal chromophore after transient termination through visual arrestin binding and the uptake of 11-cis retinal regenerates rhodopsin. In other words, the instability and bleaching properties of the rhodopsin photoproduct are responsible for the abolishment of the photoproduct and recovery of the original dark state. However, parapinopsin is converted to a photoproduct that is stable and does not bleach. Therefore, the parapinopsin photoproduct does not release the retinal chromophore and is not abolished, even under strong light. In this context, parapinopsin internalization mediated by arrestin may play an important role in photoproduct removal after transient termination by -arrestin binding in the course of recovery of the original dark state. -arrestin-mediated internalization is necessary for the selective and complete removal of the stable photoproduct from the outer segments (the signal transduction locus) for the eventual restoration of parapinopsin to its original dark state through newly synthesized parapinopsin. And also, the removal of photoproducts from the outer segments results in a decrease of parapinopsin function. This downregulation may partially contribute to the light adaptation and desensitization of photoreceptor cells, similar to the downregulation of ligand-binding GPCRs through internalization. Visual arrestins are found in a wide variety of vertebrates, including the lamprey. In most of these animals, visual arrestin is localized not only to visual cells but also to the pineal photoreceptor cells, which contain a visual pigment with bleaching property.

This suggests that most visual arrestins function along with bleaching pigments regardless of their localization. This observation strongly supports the concept of a functional combination of visual arrestin and bleaching visual pigments. Interestingly, the ascidian arrestin contains a clathrin-binding sequence and is capable of mediating internalization, similar to vertebrate -arrestin.39 Therefore, vertebrate visual arrestins appear to have diversied from their ancestral vertebrate -like arrestin, which possesses a clathrin-binding sequence and functions as a mediator of internalization, and have also evolved for function in visual cells (Figure 3). Vertebrate visual arrestin may lack a clathrin-binding domain and function as a mediator of internalization because the vertebrate visual pigments have newly acquired a bleaching property during their molecular evolution and no longer require internalization to exclude stably active photoproducts.

CONCLUSION
As described above, the opsin family are roughly divided into eight groups. Members belonging to four out of the eight groups couple to transducin, Go, Gs, and Gq, respectively, in photoreceptor cells. The varied signal phototransduction cascades are classied into two types, cyclic nucleotide signaling mediated by transducin, Go or Gs in ciliary photoreceptor cells and phosphoinositol signaling mediated by Gq in rhabdomeric photoreceptor cells. Among the cascades, transducin-mediated one involves signaling proteins specic largely to vertebrate vision. As we discussed above, acquisition of bleaching property during molecular evolution of vertebrate visual pigment might promote emergence of visual arrestin. Thus, we can predict that the bleaching property of opsin-based pigment might facilitate molecular evolution of other signaling proteins that specically couples to bleaching visual pigments. To elucidate coevolution of signaling proteins including opsins could be an important issue for understanding of evolution of molecular basis of vertebrate vision as a systems evolution.

REFERENCES
1. Terakita A. The opsins. Genome Biol 2005, 6:213. 2. Tsukamoto H, Terakita A. Diversity and functional properties of bistable pigments. Photochem Photobiol Sci 2010, 9:14351443. 3. Koyanagi M, Takano K, Tsukamoto H, Ohtsu K, Tokunaga F, Terakita A. Jellysh vision starts with cAMP signaling mediated by opsin-G(s) cascade. Proc Natl Acad Sci U S A 2008, 105:1557615580. 4. Yau KW, Hardie RC. Phototransduction motifs and variations. Cell 2009, 139:246264. 5. Kojima D, Terakita A, Ishikawa T, Tsukahara Y, Maeda A, Shichida Y. A novel Go-mediated

Vo lu me 1, Jan u ary/Febru ary 2012

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

109

Focus Article

wires.wiley.com/mts

phototransduction cascade in scallop visual cells. J Biol Chem 1997, 272:2297922982. 6. Koyanagi M, Terakita A, Kubokawa K, Shichida Y. Amphioxus homologs of Go-coupled rhodopsin and peropsin having 11-cis- and all-trans-retinals as their chromophores. FEBS Lett 2002, 531:525528. 7. Gomez MP, Nasi E. Light transduction in invertebrate hyperpolarizing photoreceptors: possible involvement of a Go-regulated guanylate cyclase. J Neurosci 2000, 20:52545263. 8. Koyanagi M, Terakita A. Gq-coupled rhodopsin subfamily composed of invertebrate visual pigment and melanopsin. Photochem Photobiol 2008, 84:10241030. 9. Huang J, Liu CH, Hughes SA, Postma M, Schwiening CJ, Hardie RC. Activation of TRP channels by protons and phosphoinositide depletion in Drosophila photoreceptors. Curr Biol 2010, 20:189197. 10. Hardie RC, Raghu P. Visual transduction Drosophila. Nature 2001, 413:186193. in

non-image-forming photic responses in blind mice. Science 2003, 301:525527. 21. Qiu X, Kumbalasiri T, Carlson SM, Wong KY, Krishna V, Provencio I, Berson DM. Induction of photosensitivity by heterologous expression of melanopsin. Nature 2005, 433:745749. 22. Arendt D. Evolution of eyes and photoreceptor cell types. Int J Dev Biol 2003, 47:563571. 23. Eakin RM. Evolution of photoreceptors. Cold Spring Harb Symp Quant Biol 1965, 30:363370. 24. Arendt D, Tessmar-Raible K, Snyman H, Dorresteijn AW, Wittbrodt J. Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain. Science 2004, 306:869871. 25. Nagata T, Koyanagi M, Tsukamoto H, Terakita A. Identication and characterization of a protostome homologue of peropsin from a jumping spider. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2010, 196:5159. 26. Yamashita T, Ohuchi H, Tomonari S, Ikeda K, Sakai K, Shichida Y. Opn5 is a UV-sensitive bistable pigment that couples with Gi subtype of G protein. Proc Natl Acad Sci U S A 2010, 107:2208422089. 27. Terakita A, Koyanagi M, Tsukamoto H, Yamashita T, Miyata T, Shichida Y. Counterion displacement in the molecular evolution of the rhodopsin family. Nat Struct Mol Biol 2004, 11:284289. 28. Koyanagi M, Kawano E, Kinugawa Y, Oishi T, Shichida Y, Tamotsu S, Terakita A. Bistable UV pigment in the lamprey pineal. Proc Natl Acad Sci U S A 2004, 101:66876691. 29. Pitt GA, Collins FD, Morton RA, Stok P. Studies on rhodopsin. VIII. Retinylidenemethylamine, an indicator yellow analogue. Biochem J 1955, 59:122128. 30. Hargrave PA, McDowell JH, Curtis DR, Wang JK, Juszczak E, Fong SL, Rao JK, Argos P. The structure of bovine rhodopsin. Biophys Struct Mech 1983, 9:235244. 31. Findlay JB, Pappin DJ. The opsin family of proteins. Biochem J 1986, 238:625642. 32. Sakmar TP, Franke RR, Khorana HG. Glutamic acid113 serves as the retinylidene Schiff base counterion in bovine rhodopsin. Proc Natl Acad Sci U S A 1989, 86:83098313. 33. Zhukovsky EA, Oprian DD. Effect of carboxylic acid side chains on the absorption maximum of visual pigments. Science 1989, 246:928930. 34. Nathans J. Determinants of visual pigment absorbance: role of charged amino acids in the putative transmembrane segments. Biochemistry 1990, 29:937942. 35. Terakita A, Yamashita T, Shichida Y. Highly conserved glutamic acid in the extracellular IV-V loop in rhodopsins acts as the counterion in retinochrome, a member of the rhodopsin family. Proc Natl Acad Sci U S A 2000, 97:1426314267.

11. Provencio I, Jiang G, De Grip WJ, Hayes WP, Rollag MD. Melanopsin: an opsin in melanophores, brain, and eye. Proc Natl Acad Sci U S A 1998, 95:340345. 12. Terakita A, Tsukamoto H, Koyanagi M, Sugahara M, Yamashita T, Shichida Y. Expression and comparative characterization of Gq-coupled invertebrate visual pigments and melanopsin. J Neurochem 2008, 105:883890. 13. Rollag MD, Berson DM, Provencio I. Melanopsin, ganglion-cell photoreceptors, and mammalian photoentrainment. J Biol Rhythms 2003, 18:227234. 14. Fu Y, Liao HW, Do MT, Yau KW. Non-image-forming ocular photoreception in vertebrates. Curr Opin Neurobiol 2005, 15:415422. 15. Hankins MW, Peirson SN, Foster RG. Melanopsin: an exciting photopigment. Trends Neurosci 2008, 31:2736. 16. Bailes HJ, Lucas RJ. Melanopsin and inner retinal photoreception. Cell Mol Life Sci 2010, 67:99111. 17. Koyanagi M, Kubokawa K, Tsukamoto H, Shichida Y, Terakita A. Cephalochordate melanopsin: evolutionary linkage between invertebrate visual cells and vertebrate photosensitive retinal ganglion cells. Curr Biol 2005, 15:10651069. 18. Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci 2001, 4:621626. 19. Hattar S, Lucas RJ, Mrosovsky N, Thompson S, Douglas RH, Hankins MW, Lem J, Biel M, Hofmann F, Foster RG, et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 2003, 424:7681. 20. Panda S, Provencio I, Tu DC, Pires SS, Rollag MD, Castrucci AM, Pletcher MT, Sato TK, Wiltshire T, Andahazy M, et al. Melanopsin is required for

110

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

Vo lu me 1, Jan u ary/Febru ary 2012

WIREs Membrane Transport and Signaling

Evolution and diversity of opsins

36. Tsukamoto H, Farrens DL, Koyanagi M, Terakita A. The magnitude of the light-induced conformational change in different rhodopsins correlates with their ability to activate G proteins. J Biol Chem 2009, 284:2067620683. 37. Do MT, Kang SH, Xue T, Zhong H, Liao HW, Bergles DE, Yau KW. Photon capture and signalling by melanopsin retinal ganglion cells. Nature 2009, 457:281287. 38. Scott K, Zuker CS. Assembly of the Drosophila phototransduction cascade into a signalling complex shapes elementary responses. Nature 1998, 395:805808. 39. Nakagawa M, Orii H, Yoshida N, Jojima E, Horie T, Yoshida R, Haga T, Tsuda M. Ascidian arrestin (Ciarr), the origin of the visual and nonvisual arrestins of vertebrate. Eur J Biochem 2002, 269:51125118. 40. Kawano-Yamashita E, Koyanagi M, Shichida Y, Oishi T, Tamotsu S, Terakita A. -arrestin functionally regulates the non-bleaching pigment parapinopsin in lamprey pineal. PLoS ONE 2011, 6:e16402. 41. Kawano-Yamashita E, Terakita A, Koyanagi M, Shichida Y, Oishi T, Tamotsu S. Immunohistochemical characterization of a parapinopsin-containing

photoreceptor cell involved in the ultraviolet/green discrimination in the pineal organ of the river lamprey Lethenteron japonicum. J Exp Biol 2007, 210(Pt 21):38213829. 42. Ferguson SS, Barak LS, Zhang J, Caron MG. G-proteincoupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins. Can J Physiol Pharmacol 1996, 74:10951110. 43. Ferguson SS, Downey WE 3rd, Colapietro AM, Barak LS, Menard L, Caron MG. Role of -arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 1996, 271:363366. 44. Goodman OB Jr, Krupnick JG, Santini F, Gurevich VV, Penn RB, Gagnon AW, Keen JH, Benovic JL. -arrestin acts as a clathrin adaptor in endocytosis of the 2adrenergic receptor. Nature 1996, 383:447450. 45. Krupnick JG, Benovic JL. The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol 1998, 38:289319. 46. Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. -Arrestin: a protein that regulates -adrenergic receptor function. Science 1990, 248:15471550.

Vo lu me 1, Jan u ary/Febru ary 2012

2012 WIL EY-VCH Verlag GmbH & Co. K GaA, Wein h eim.

111