Molecular evolution of proteins involved in vertebrate phototransduction

Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Review

Molecular evolution of proteins involved in vertebrate phototransduction夞 Osamu Hisatomi*, Fumio Tokunaga Department of Earth and Space Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan Received 27 April 2002; received in revised form 15 July 2002; accepted 20 July 2002

Abstract Vision is one of the most important senses for vertebrates. As a result, vertebrates have evolved a highly organized system of retinal photoreceptors. Light triggers an enzymatic cascade, called the phototransduction cascade, that leads to the hyperpolarization of photoreceptors. It is expected that a systematic comparison of phototransduction cascades of various vertebrates can provide insights into the diversity of vertebrate photoreceptors and into the evolution of vertebrate vision. However, only a few attempts have been made to compare each phototransduction protein participating in this cascade. Here, we determine phylogenetic trees of the vertebrate phototransduction proteins and compare them. It is demonstrated that vertebrate opsin sequences fall into five fundamental subfamilies. It is speculated that this is crucial for the diversity of the spectral sensitivity observed in vertebrate photoreceptors and provides the vertebrates with the molecular tools to discriminate the color of incident light. Other phototransduction proteins can be classified into only a few subfamilies. Cones generally share isoforms of phototransduction proteins that are different from those found in rods. The difference in sensitivity to light between rods and cones is likely due to the difference in the molecular properties of these isoforms. The phototransduction proteins seem to have co-evolved as a system. Switching the expression of these isoforms may characterize individual vertebrate photoreceptors. 䊚 2002 Elsevier Science Inc. All rights reserved. Keywords: Phototransduction; Molecular evolution; Visual system; Opsin; Photoreceptor

1. Introduction 1.1. Diversity found in vertebrate photoreceptors Vision is one of the most important senses for vertebrates. As a result, vertebrates have evolved a highly organized system of light detection. At the first stage of vision, photons incident on the eye are captured by photoreceptors in the retina, 夞 Contribution to a special issue of CBP on Comparative Functional Genomics. *Corresponding author. Tel.: q81-6-6850-5500; fax: q816-6850-5480. E-mail address: [email protected] (O. Hisatomi).

leading to hyperpolarization of the photoreceptor membrane. This electrochemical response is transmitted to the brain via higher-order neurons. To receive light under a variety of photic environments, vertebrates have evolved photoreceptors having distinct characters. Two kinds of variability are generally found among vertebrate photoreceptors. One is the diversity in the range of light intensities detectable by each photoreceptor, that is the sensitivity to light. Many vertebrates have duplicate photoreceptor types (rods and cones) responsible for twilight and daylight vision, respectively. Rods and cones have different characters corresponding to their physiological functions:

1096-4959/02/$ - see front matter 䊚 2002 Elsevier Science Inc. All rights reserved. PII: S 1 0 9 6 - 4 9 5 9 Ž 0 2 . 0 0 1 2 7 - 6

510

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

cones are less sensitive than rods. The light response of cones is faster and is terminated more rapidly than that of rods (Baylor, 1987; Tachibanaki et al., 2001), with more pronounced adaptation than rods (Normann and Werblin, 1974). These two photoreceptor types help us to detect light over a wide range of intensities. The other diversity is the wavelength of light sensitivity of each photoreceptor, that is the spectral sensitivity. Many vertebrates have multiple cones of different spectral sensitivity and utilize them for the discrimination of colors of incident light. 1.2. Phototransduction cascade Most biological functions are accomplished by an appropriate system consisting of multiple proteins. The phototransduction cascade (an enzymatic cascade) in vertebrate photoreceptors is one of the representative systems. Photons captured in the outer segments of the photoreceptor trigger the cascade, resulting in closure of a fraction of the cGMP-gated channels in the cell membrane (for a review, see Hargrave and McDowell, 1992; Pepe, 2001). Many researchers have intensively studied the phototransduction proteins participating in this cascade and the interactions between them. However, most of the studies carried out at the molecular level have focused on individual phototransduction proteins found in certain mammalian rods. The phototransduction cascades in non-mammalian rods, particularly those observed in cones, are less well understood. However, cones possess similar phototransduction proteins, suggesting that the signal transduction pathway of vertebrate photoreceptors is essentially identical (for review, see Ebrey and Koutalos, 2001). Recent advances in molecular biological techniques have facilitated the isolation of cDNAs and genomic DNAs encoding phototransduction proteins. The number of available sequence data is rapidly growing. It is expected that a systematic comparison of the phototransduction cascades in various vertebrates can provide insights into the diversity of vertebrate photoreceptors and into the evolution of vertebrate vision. However, only a few reports attempt to compare the whole phototransduction system on a molecular level (Ebrey and Koutalos, 2001). Here, we summarize the molecular evolution of each vertebrate phototransduction protein and compare them. The fundamental system of

vertebrate phototransduction that an ancestral vertebrate may have possessed is then discussed. 2. Diversity of spectral sensitivity 2.1. Vertebrate visual pigments First we focus on the diversity of spectral sensitivity of vertebrate photoreceptors. The spectral sensitivity of photoreceptors is mainly due to the absorption spectrum of its visual pigment, consisting of the chromophore (11-cis-retinal) and the protein moiety (opsin) (Fig. 1). The absorption spectra of vertebrate visual pigments have similar shapes (Lamb, 1995). The spectral sensitivity can therefore be represented by the wavelength of maximum absorbance (absorption maximum or lmax). Some vertebrate pigments naturally have 3dehydro-retinal (retinal2 ) instead of retinal1 as the chromophore. The lmax values of the pigments are shifted to a shorter wavelength by exchanging the chromophore from retinal2 to retinal1 . The lmax of retinal1-based pigment can be estimated from that ´ of retinal2-based pigment (Harosi, 1994). In this manuscript, we focus on the interaction between opsin and chromophore, and therefore consider only retinal1-based pigments. It should be noted that, even if only retinal1-based pigments are being taken into consideration, the lmax values of vertebrate visual pigments are widely distributed from 350 to 570 nm. This diversity is likely caused by the difference in the chromophore–opsin interaction, and can be understood on the basis of a detailed analysis of opsin sequences (Yokoyama, 1995, 2000). 2.2. Phylogeny of vertebrate opsin sequences Since Nathans and Hogness (1983) reported the nucleotide sequence of the bovine rhodopsin gene, cDNAs and genomic DNAs encoding various vertebrate opsins have been isolated. Humans have rhodopsin (lmax at 496 nm) and three kinds of cone pigments, blue-, green- and red-sensitive pigments with lmax at 419, 531 and 558 nm, respectively (Dartnall et al., 1983). The identity of amino acid sequences between the human redand green-sensitive pigments is 96%, and it is estimated that these two genes have diverged relatively recently (Nathans et al., 1986; Yokoyama and Yokoyama, 1990). We can therefore recognize three human opsin groups, which, in this

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

511

Fig. 1. Two-dimensional model of bovine rhodopsin modified from Hargrave and McDowell (1992). 11-cis-Retinal (gray lines) bound to a lysine residue (K296; black circle) is also illustrated. Glycosylated asparagines (N2 and N15), palmitoylated cysteines (C322 and C323) and cysteines forming a disulfide bond (C110 and 187) are shaded. The absorption maxima of the pigments are tuned by amino acids in the opsin sequences.

paper, will be referred to as ‘LWS’ (red- and green-sensitive pigments), ‘RH1’ (rhodopsin) and ‘SWS1’ (blue-sensitive pigment), based on the nomenclature used by Yokoyama and co-workers (Yokoyama, 1995, 2000; Ebrey and Koutalos, 2001). Other groups, RH2 and SWS2, have been found in studies of chicken and teleost opsins (Okano et al., 1992; Johnson et al., 1993; Hisatomi et al., 1994). More than 100 amino acid sequences of vertebrate opsins have been deposited in the databases so far. A molecular phylogenetic tree calculated by the neighbor-joining (NJ) method (Saitou and Nei, 1987) from the amino acid sequences of representative vertebrate opsins is shown in Fig. 2a. Except for some special cases, such as dg4 opsin, similar to pinopsin found in a diurnal gecko (Taniguchi et al., 2001), it is suggested that vertebrate opsins can be classified into five fundamental subfamilies. It seems reasonable to assume that ancestral vertebrates had five opsins belonging to these fundamental subfamilies, because lamprey has an opsin that clearly falls into the RH1 subfamily (Hisatomi et al., 1991; Zhang and Yokoyama, 1997). However, some vertebrates do not have any opsins classified into one or two of the groups: RH2 opsins have not been found in amphibians and mammals, and SWS2 opsins have not been reported in mammals. Moreover, geckos seem to

have lost the RH1 and SWS2 opsins (Taniguchi et al., 2001). Why do RH2 and SWS2 opsins readily disappear in many vertebrates? The phylogenetic tree predicts that LWS and SWS1 opsins diverged earlier from other subfamilies, and that the remaining SWS2, RH2 and RH opsins have branched afterward. This led us to speculate that either the RH1 or RH2 opsins were the easiest to be lost, and that either the remaining RH1yRH2 opsin or SWS2 opsin followed. However, there seems to be a functional constraint maintaining the rod isoforms, including RH1 opsins (rhodopsin), as discussed in the later sections. 2.3. Relationships between opsin subfamilies and the spectral sensitivity of pigments Fig. 2b indicates the distribution of lmax of retinal1-based pigments belonging to each of the subfamilies known so far. Although the lmax of vertebrate retinal1-based pigments covers the range from 350 to 570 nm, the distribution of lmax of the pigments belonging to the same subfamily is within 100 nm. The clear relationship between the spectral sensitivity and these five subfamilies suggests that the presence of five fundamental opsin subfamilies is essential for the uptake of a wider range of wavelength of light, thus providing the vertebrates with molecular tools for color discrim-

512

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Fig. 2. (a) A dendrogram of representative vertebrate opsins calculated by the NJ method using the amino acid sequence of Drosophila RH1 (P06002) as an outgroup. The number in parentheses represents the accession number of each sequence. The bars represent the substitution rate (ks0.1) of each amino acid. (b) The distribution of lmax of retinal1-based pigments belonging to each fundamental subfamily.

ination. It should be emphasized that the phylogenetic analysis of opsin sequences gives us clues to understanding the diversity in spectral sensitivity. 3. Excitation of the phototransduction cascade 3.1. Molecular mechanism for light excitation Most of the current knowledge on the molecular mechanism of phototransduction has been obtained through studies of mammalian rods. Light induces the cis–trans isomerization of 11-cis-retinal, leading to the conformational change of rhodopsin to an activated state (for review, see Hargrave and McDowell, 1992). Photoactivated rhodopsin interacts with the photoreceptor-specific heterotrimeric GTP-binding protein, transducin (designated as Gt or Gtabg) composed of a, b and g subunits. This

enables exchange of GDP bound to Gt by GTP (Hamm and Gilchrist, 1996) (Fig. 3). The GTPconjugated a subunit of Gt (Gta–GTP) dissociates from the bg subunit (Gtbg) and binds to an inhibitory subunit of cGMP–phosphodiesterase (PDE). It activates the PDE in the rod outer segments (ROS) and increases the rate of cGMP hydrolysis. The decrease in intracellular cGMP concentration induces the closure of the cGMPgated cation channels on the cell membrane, and results in hyperpolarization of the rods (see review Arshavsky et al., 2002). 3.2. Transducin (Gt) Since 1985, when four primary structure of Gta (Gtra) in bovine rod outer al., 1985; Medynski et al.,

groups reported the designated as Gt1a segments (Lochrie et 1985; Tanaba et al.,

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

513

Fig. 3. A schematic drawing of the phototransduction cascade in the rod outer segments of vertebrates. A similar cascade is believed to be present in cones. Solid, white and broken lines represent the activation, deactivation and adaptation pathways, respectively.

1985; Yatsunami and Khorana, 1985), cDNAs encoding Gta have been isolated from several vertebrates, mammals, chicken, salamander and zebrafish. Our BLAST search yielded 14 full-length Gta sequences with high scores (Altschul et al., 1997) using the bovine Gt1a sequence as a probe. Fig. 4a shows the dendrogram of Gta, which indicates two subfamilies of vertebrate Gta, Gt1a (Gtra) and Gt2a (Gtca). An immunohistochemical study demonstrated that bovine Gt1a and Gt2a are selectively expressed in rods and cones, respectively (Lerea et al., 1986). In the human retina, Gt2a is present in all blue-, green-, and redsensitive cones (Lerea et al., 1989), suggesting that Gt1 and Gt2 are rod- and cone-specific isoforms, respectively. In addition to Gta, bovine rods and cones express different Gtbg isoforms: Gb1 and Gg1 exist in rods, whereas Gb3 and Gg8 exist in cones (Ong et al., 1997). It remains unclear whether these Gb and Gg isoforms are selectively expressed in either rods or cones of other vertebrates, and whether these isoforms have any differences in molecular properties.

inhibitory g subunits (PDEg) (Baehr et al., 1979; Deterre et al., 1988). In contrast, it has been reported that the PDE in cones are composed of two identical catalytic a9 subunits, two inhibitory g subunits, and two additional components with molecular masses of 13 and 15 kDa (Gillespie and Beavo, 1988). A total of 15 sequences of putative catalytic subunits of vertebrate photoreceptor PDEs are found in the database. The amino acid sequences of the a and b subunits share approximately 80% identity, but lower identity is shown between a (or b) and a9 subunits. Fig. 4b is a dendrogram of the PDE catalytic subunits of mammals and of the leopard frog. It is suggested that cone-type a9 subunits have diverged from an ancestral rod-type subunit and that the a and b subunits have been duplicated. It has been reported that the dissociation constants of non-catalytic cGMP-binding sites are less than 1 nM for rod PDE and approximately 11 nM for cone PDE (Gillespie and Beavo, 1988). This may contribute to the efficiency of cGMP hydrolysis between rod and cone isoforms. 3.4. cGMP-gated channel

3.3. Phosphodiesterase (PDE) Photoreceptor cGMP phosphodiesterase (PDE) in bovine rods is a heterohexamer consisting of two catalytic subunits (a and b subunits) and two

The cyclic nucleotide (cGMP)-gated channels (CNGs) in bovine rods consist of two subunits, a and b, with a molecular mass of approximately 63 and 240 kDa, respectively (Cook et al., 1987;

514

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Fig. 4. Dendrograms of vertebrate phototransduction proteins: (a) transducin a-subunit (Gta); (b) phosphodiesterase (PDE); (c) cGMPgated channel; (d) opsin kinase; (e) arrestin; (f) guanylate cyclase (GC) (kinase-homology and catalytic domains); (g) S-modulinyrecoverin; and (h) GC-activating protein (GCAP). Rooted trees were calculated by NJ-method using phylogenetically closely related sequences as outgroups: Gta, human Gi2 (P04899); PDE, human CN4D Q08499; channel, mouse of CNG2 (Q62398); kinase, human GRK4a (U33054); arrestin, human b-arrestin2 (P32121); GC, human ANP-B (P20594); S-modulinyrecoverin, human VILIP-1 (P42323); GCAP, human recoverin (P35243). The numbers in parentheses represent the accession number of each sequence. Broken lines in (f) indicate the topology with considerable ambiguity. Each of these phototransduction proteins forms a single cluster, even if other phylogenetically related sequences of non-visual proteins or invertebrate phototransduction proteins are taken into consideration. The bars represent the substitution rate (ks0.1) of each amino acid.

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Molday et al., 1990). The a subunit (designated as CNG1) can form a cGMP-sensitive channel, and the b subunit mediates Ca2q –calmodulin (CAM) modulation (Hsu and Molday, 1993; Chen et al., 1994). Kaupp et al. (1989) first reported the bovine CNG1 sequence; another type of CNG, ¨ CNG3, has been found in cones (Bonigk et al., 1993). A total of 10 CNG sequences can be found in the databases. These fall into the CNG1 and CNG3 groups (Fig. 4c). However, channel sequences have only been investigated in mammals and in chicken, and therefore it is possible that another subtype may be found in other vertebrates. Unlike the cGMP-gated channels in rods, cone channels are not modulated by Ca2q –CAM (Haynes and Stotz, 1997). They are also more permeable to Ca2q than the rod channel, which seems to result in light-dependent changes in cytoplasmic Ca2q concentrations that are larger and faster in cones than in rods (Frings et al., 1995; Picones and Korenbrot, 1995). 4. Deactivation of phototransduction cascade 4.1. Molecular mechanisms for deactivation from light excitation In each step of the light excitation process, there are mechanisms for deactivation from light excitation (Fig. 3). Activated rhodopsin intermediate metarhodopsin II is phosphorylated by rhodopsin kinase (Kuhn, 1984), and arrestin binds to the phosphorylated rhodopsin, precluding further activation of transducin (Palczewski, 1994). Gt and PDE are inactivated as follows. The GTP bound to Gta is hydrolyzed by the intrinsic GTPase activity of Gta, and a regulator of G-protein signaling (RGS9) accelerates the GTPase activity (He et al., 1998). The consequent inactive Gta– GDP releases the inhibitory subunit, PDEg, and the PDE is then inactivated. The intracellular cGMP concentration is restored to the initial level by the activity of retinal guanylate cyclases (GCs) in the ROS wPugh et al., 1997x. Recently, it has been reported that RGS9 inhibits GC activity and may serve as a mediator between the PDE and GC systems (Seno et al., 1998). 4.2. Opsin kinases Rhodopsin kinase, GRK1, is one of the beststudied G-protein-coupled receptor kinases

515

(GRKs). It has been reported that the mammalian GRK1 is localized on the outer segments of both rods and cones (Palczewski et al., 1993; Zhao et al., 1998), and is anchored to the membrane with its farnesylated C-terminal (Inglese et al., 1992a). A novel GRK subtype (GRK7) was found in the medaka retina, and it is suggested that GRK7 is expressed in all four subtypes of medaka cones that express distinct opsin subtypes. This is deduced by taking advantage of the fact that cones in teleost fish are morphologically distinguishable and arranged in species-specific mosaic patterns (Hisatomi et al., 1998). In addition, GRK7 has been found in mammals (Weiss et al., 1998), but species-specific differences in expression of GRK1 and GRK7 were observed in mammalian cones (Chen et al., 2001; Weiss et al., 2001). Fig. 4d shows a dendrogram calculated 11 sequences that were revealed by our BLAST search. GRK1 and GRK7 appear to have diverged before the teleost– tetrapod divergence. Unlike GRK1, the C-terminal of GRK7 has a consensus sequence for geranylgeranylation (Hisatomi et al., 1998; Weiss et al., 1998). This may elevate the efficiency of phosphorylation and decrease the lifetime of lightactivated cone pigments (Inglese et al., 1992b). 4.3. Arrestin Since Wistow et al. (1986) reported the sequence of bovine arrestin (S-antigen) cDNA, amino acid sequences of 16 vertebrate visual arrestins can be found in the databases. These arrestin sequences fall into two groups (Fig. 4e). One group includes the bovine S-antigen and the other group contains the cone-type arrestins of human (X-arrestin and C-arrestin), frog and medaka (Murakami et al., 1993; Craft et al., 1994; Craft and Whitmore, 1995; Abdulaeva et al., 1995; Hisatomi et al., 1997). By immunohistochemical experiments, it has been suggested that X-arrestin is expressed in red-, green- and blue-sensitive cones in the human retina (Sakuma et al., 1996). In situ hybridization demonstrated that all four types of medaka cones share the same arrestin isoform, distinct from that of rods (Hisatomi et al., 1997). However, it has been reported that blue cones of certain mammals have epitopically similar arrestins to those of rods (Nir and Ransom, 1992) and two arrestin isoforms are co-expressed in medaka rods (Imanishi et al., 1999). Swapping and coexistence of arrestins isoforms probably took

516

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

place without a significant loss of photoreceptor function. It remains unclear whether there are some physicochemical differences between rod and cone isoforms. 4.4. RGS9 RGS9 is a regulator of G-protein signaling required for a rapid recovery of light response in vertebrate photoreceptors (He et al., 1998). Because only four mammalian RGS9 have been reported so far, it is unclear whether only one kind of RGS9 isoform plays a role in phototransduction cascades in non-mammalian photoreceptors. However, it should be noted that RGS9 is expressed in both rods and cones, but is present in cones at significantly higher levels than in rods (Cowan et al., 1998). The RGS9 concentration emerges as a potentially important determinant of the faster response kinetics and lower sensitivity of mammalian cones compared to rods (Cowan et al., 1998). 4.5. Guanylate cyclase (GC) Two kinds of photoreceptor GCs, GC1 and GC2, have been identified in the human retina (Shyjan et al., 1992; Lowe et al., 1995). GC1 is primarily localized in cone outer segments (COS) and to a lesser extent in rod outer segments (ROS) (Dizhoor et al., 1994; Liu et al., 1994). GC2 appears to be expressed in both rods and cones (Shyjan et al., 1992; Imanishi et al., 2002). In the medaka retina, two kinds of GC isoforms are likely co-expressed in rods, and another GC isoform is expressed in all four types of cones (Seimiya et al., 1997; Hisatomi et al., 1999). Analysis of 12 photoreceptor GC sequences of mammals and medaka suggests the existence of at least three subfamilies of vertebrate photoreceptor GCs (Fig. 4f). However, a large ambiguity is found in the tree topology. This may be due to coevolution with GC-activating proteins (see later section). 5. Adaptation mediated by Ca2H 5.1. Molecular mechanism for adaptation Vertebrate photoreceptor cells have a negative feedback light-adaptation mechanism mediated by Ca2q. In the dark-adapted photoreceptors, the

cGMP-gated cation channels are opened and Ca2q flows into the cell (Stryer, 1986; Kaupp and Koch, 1992). Intracellular Ca2q is continuously pumped out by a Naq-Kq yCa2q exchanger (NCKX) in the outer segment (Yau and Nakatani, 1985; Cervetto et al., 1989). Light initiates the phototransduction cascade, closes the cation channels and blocks the Ca2q influx. The result is a cytoplasmic Ca2q concentration decrease in the light-adapted state (Matthews, et al., 1988; Nakatani and Yau, 1988). A frog photoreceptor Ca2qbinding protein, S-modulin, and its bovine homologue, recoverin, inhibit the phosphorylation of light-activated rhodopsin at high Ca2q concentrations (Dizhoor et al., 1991; Kawamura and Murakami, 1991; Kawamura, 1993) and contribute to the increase in light sensitivity in the darkadapted state (Ratto et al., 1988; Korenbrot and Miller, 1989). The decrease in intracellular Ca2q concentration inactivates a Ca2q-dependent adenylate cyclase, and the consequent decrease of cAMP concentration then inactivates the cAMPdependent protein kinase (PKA) in rods (Willardson et al., 1996). Phosducin (PD) is phosphorylated by PKA and continuously dephosphorylated by a protein phosphatase. Therefore, PD is phosphorylated in the dark-adapted rods and dephosphorylated upon illumination. Unphosphorylated PD forms a complex with Gtbg and prevents the reformation of Gtabg. This in turn decreases the amount of active Gta–GTP produced by the light-activated rhodopsin in the lightadapted rods (Lee et al., 1984; Wilkins et al., 1996). In addition, the decrease in intracellular Ca2q concentration in light-adapted rods elevates the activity of the photoreceptor GCs, which is mediated by the Ca2q-binding proteins, termed GC-activating proteins (GCAPs) (Palczewski et al., 1994). 5.2. Naq-Kq yCa2q exchanger Since Reilaender et al. (1992) reported the primary structure of the bovine photoreceptorspecific Naq-Kq yCa2q exchanger (NCKX), cDNAs encoding NCKXs have been isolated from several mammalian species. Recently, Prinsen et al. (2000) reported on cone isoforms of NCKX from human and chicken, and suggested that abundant rod NCKX transcripts were present only in rod photoreceptors, whereas abundant cone NCKX transcripts were found in most cones. The differ-

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

ence in NCKX isoforms between rods and cones may affect the kinetics of the light-stimulated decrease in Ca2q concentration, which is faster in cones than in rods (Nakatani and Yau, 1989; Hestrin and Korenbrot, 1990). 5.3. S-modulin S-modulin is a Ca2q-binding protein found in bullfrog rods (Kawamura and Murakami, 1991; Kawamura, 1993). Mammalian orthologues of Smodulin are called recoverin (Dizhoor et al., 1991; Ray et al., 1992) and are believed to be expressed in both rods and cones (Polans et al., 1991, 1993; Milam et al., 1993). It has been reported that an S-modulin homologue, termed s26, exists in bullfrog cones (Kawamura et al., 1996). These proteins have the ability to interact with rhodopsin kinase and inhibit the phosphorylation of rhodopsin at high Ca2q concentrations (Kawamura et al., 1993, 1996; Klenchin et al., 1995). Only seven sequences, closely related to that of S-modulin, are found in the databases, but the dendrogram forms two clusters. S-modulin and mammalian recoverin form one cluster, and s26 and chicken visinin form the other (Fig. 4g). S-modulin inhibits the phosphorylation of rhodopsin more efficiently than s26, due to the positively charged residues found near its C-terminus (Matsuda et al., 1999). The distribution of charged residues in the Cterminal regions of mammalian recoverin and chicken visinin are similar to those of S-modulin and s26, respectively. It is therefore speculated that S-modulin and recoverin prolong the lifetime of the active form of rhodopsin more efficiently than s26. This may contribute to their increased light sensitivity. 5.4. Phosducin (PD) It has previously been thought that only one kind of PD commonly exists in mammalian rods and cones, because only one kind of cDNA was cloned from the retina, and anti-PD antibodies recognized these photoreceptor types equally (Kuo et al., 1989; Abe et al., 1990; Watanabe et al., 1996). The one exception is an anti-bovine PD antibody showing different reactivity between blue and green cones in the ground squirrel retina (von Schantz et al., 1994). Recently, two kinds of cDNAs encoding putative PDs, selectively expressed either in rods or in all four types of

517

cones, were isolated from the medaka retina (Kobayashi et al., 2001). Immunohistochemical studies suggested that many teleosts have rod- and cone-specific PDs in their retinas (Kobayashi et al., 2001). However, it remains unclear whether or not mammals have just one PD, and why it is that teleosts have two kinds of PDs. 5.5. GCAP Palczewski et al. (1994) first reported on the amino acid sequences of human, murine, bovine and frog GCAPs (GCAP1). The second isoform of GCAP, GCAP2, was then found in mammalian retinas (Dizhoor et al., 1995; Gorczyca et al., 1995). It has been suggested that GCAP1 and GCAP2 are localized in rods and cones of mammalian retinas in a species-specific manner (Cuenca et al., 1998; Howes et al., 1998; Kachi et al., 1999; Imanishi et al., 2002). The third GCAP isoform, GCAP3, has been found in human cones, but not detected in rodents (Haeseleer et al., 1999). Knowledge of non-mammalian GCAPs is limited to the amino acid sequences of frog and chicken GCAPs (Palczewski et al., 1994; Semple-Rowland et al., 1999). Recently, cDNAs encoding the putative GCAPs were isolated from zebrafish retina, and it was demonstrated that GCAP1 and 2 are expressed in rods and short, single cones, whereas GCAP3 is in all subtypes of cones (Imanishi et al., 2002). The phylogenetic analysis of 12 GCAP sequences clearly indicates the existence of three GCAP groups (GCAP1, 2 and 3), although some ambiguity was found in their topology (Fig. 4h). In vitro, GCAP1 activates GC1 more efficiently than GC2 (Haeseleer et al., 1999; Krylov et al., 1999), whereas GCAP2 activates both GC1 and GC2 with similar efficiency (Dizhoor et al., 1994; Lowe et al., 1995; Laura and Hurley, 1998). From the analyses of GCAP knockout mice, it was suggested that GCAP1 and GCAP2 may make distinct contributions to the regulation of GC in rods (Mendez et al., 2001). 6. Summary Except for opsin, 11 phototransduction proteins discussed in this manuscript can be classified into a few subfamilies. Six vertebrate phototransduction proteins, Gt, cGMP-gated channels, opsin kinases, S-modulins (recoverins), arrestins and Naq-Kq y Ca2q exchangers fall into two fundamental sub-

518

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Fig. 5. A model showing the fundamental system of vertebrate phototransduction, which generates the diversities of individual photoreceptors. Only switching the expression of opsin genes in cones can change the spectral sensitivity. Selective expression of the phototransduction protein isoforms is responsible for the diversity of the sensitivity to light for individual photoreceptors. When cone isoforms of phototransduction proteins and RH2 opsin are selectively expressed, the photoreceptor functions as a green-sensitive photoreceptor with low sensitivity to light.

families, which include isoforms selectively expressed in either rods or cones. PDE and GCAP can be divided into three subfamilies, two of which contain isoforms co-expressed in rods. Each of these phototransduction proteins forms a single cluster, even if other phylogenetically related sequences of non-visual proteins or invertebrate phototransduction proteins are taken into consideration. It is likely that the gene duplications causing these subfamilies have occurred after the formation of the prototype of the vertebrate phototransduction cascade. Moreover, these subfamilies have apparently duplicated before the teleost– tetrapod divergence. The similarity of the dendrograms among the phototransduction proteins suggests that these subfamilies have arisen from a large gene duplication, including whole phototransduction genes, andyor by co-evolution of phototransduction proteins as a system. Molecular biological studies on vertebrate opsins have revealed the existence of five fundamental subfamilies essential for taking up a wider range of wavelength of light. In most cases, cones share the same isoforms of phototransduction proteins, even cones possessing distinct opsin subtypes. The spectral sensitivity of cones is likely determined only by the switching of opsin expression. We can therefore speculate on the fundamen-

tal system of vertebrate phototransduction, as shown in Fig. 5. An ancestral vertebrate may have possessed a similar system. Most of the studies carried out to date suggest that cone isoforms can function in a phototransduction system of rods. For example, cone opsins can activate rod transducin (Gt1) (Imai et al., 1997) and s26 can inhibit rhodopsin kinase activity (Kawamura et al., 1996). Recently, Ma et al. (2001) reported that the salamander SWS2 opsin is expressed in both rods and cones, in which it couples with rod and cone isoforms of G-proteins, Gt1 and Gt2, respectively. It is suggested that rod and cone isoforms can be swapped without a significant loss of photoreceptor function. Why then did many vertebrates maintain rod and cone isoforms during their evolution over hundreds of millions of years? It seems reasonable to assume that these isoforms possess certain differences responsible for the diversity of sensitivity to light between rods and cones. Indeed, detailed analyses on phototransduction proteins revealed the difference in molecular properties of these isoforms that may influence their physiological responses between rods and cones (Imai et al., 1997; Matsuda et al., 1999; Tachibanaki et al., 2001). Isoforms and their selective expression may characterize individual photoreceptors, thus pro-

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

viding us with physiological functions such as color vision and daylightytwilight vision. Acknowledgments This work was supported by Special Coordination Funds for Promoting Science and Technology (SCF) and by a Grant-in-Aid for Scientific Research. References Abe, T., Nakabayashi, H., Tamada, H., et al., 1990. Analysis of the human, bovine and rat 33-kDa proteins and cDNA in retina and pineal gland. Gene 91, 209–215. Abdulaeva, G., Hargrave, P.A., Smith, W.C., 1995. The sequence of arrestins from rod and cone photoreceptors in the frogs Rana catesbeiana and Rana pipiens. Localization of gene transcripts by reverse-transcription polymerase chain reaction on isolated photoreceptors. Eur. J. Biochem. 234, 437–442. Altschul, S.F., Madden, T.L., Schaffer, A.A., et al., 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402. Arshavsky, V.Y., Lamb, T.D., Pugh, E.N., 2002. G proteins and phototransduction. Annu. Rev. Physiol. 64, 153–187. Baehr, W., Devlin, M.J., Applebury, M.L., 1979. Isolation and characterization of cGMP phosphodiesterase from bovine rod outer segments. J. Biol. Chem. 254, 11677–11699. Baylor, D.A., 1987. Photoreceptor signals and vision. Proctor Lecture. Invest. Opthalmol. Vis. Sci. 28, 34–49. ¨ Bonigk, W., Altenhofen, W., Muller, F., et al., 1993. Rod and cone photoreceptor cells express distinct genes for cGMPgated channels. Neuron 10, 865–867. Cervetto, L., Lagnado, L., Perry, R.J., Robinson, D.W., McNaughton, P.A., 1989. Extrusion of calcium from rod outer segments is driven by both sodium and potassium gradients. Nature 337, 740–743. Chen, C.K., Zhang, K., Church-Kopish, J., et al., 2001. Characterization of human GRK7 as a potential cone opsin kinase. Mol. Vis. 7, 305–313. Chen, T.Y., Illing, M., Molday, L.L., Hsu, Y.T., Yau, K.W., Molday, R.S., 1994. Subunit 2 (or b) of retinal rod cGMPgated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca2q –calmodulin modulation. Proc. Natl. Acad. Sci. USA 91, 11757–11761. Cook, N.J., Hanke, W., Kaupp, U.B., 1987. Identification, purification, and functional reconstitution of the cyclic GMP-dependent channel from rod photoreceptors. Proc. Natl. Acad. Sci. USA 84, 585–589. Cowan, C.W., Fariss, R.N., Sokal, I., Palczewski, K., Wensel, T.G., 1998. High expression levels in cones of RGS9, the predominant GTPase accelerating protein of rods. Proc. Natl. Acad. Sci. USA 95, 5351–5356. Craft, C.M., Whitmore, D.H., 1995. The arrestin superfamily: cone arrestins are a fourth family. FEBS Lett. 362, 247–255. Craft, C.M., Whitmore, D.H., Wiechmann, A.F., 1994. Cone arrestin identified by targeting expression of a functional family. J. Biol. Chem. 269, 4613–4619.

519

Cuenca, N., Lopez, S., Howes, K., Kolb, H., 1998. The localization of guanylyl cyclase-activating proteins in the mammalian retina. Invest. Ophthalmol. Vis. Sci. 39, 1243–1250. Dartnall, H.J.A., Bowmaker, J.K., Mollon, J.D., 1983. Human visual pigments: microspectrophotometric results from the eyes of seven persons. Proc. R. Soc. Lond. B 220, 115–130. Deterre, P., Bigay, J., Forquet, F., Robert, M., Chabre, M., 1988. cGMP phosphodiesterase of retinal rods is regulated by two inhibitory subunits. Proc. Natl. Acad. Sci. USA 85, 2424–2428. Dizhoor, A.M., Ray, S., Kumar, S., et al., 1991. Recoverin: a calcium-sensitive activator of retinal rod guanylate cyclase. Science 251, 915–918. Dizhoor, A.M., Lowe, D.G., Olshevskaya, E.V., Laura, R.P., Hurley, J.B., 1994. The human photoreceptor membrane guanylyl cyclase, RetGC, is present in outer segments and is regulated by calcium and a soluble activator. Neuron 12, 1345–1352. Dizhoor, A.M., Olshevskaya, E.V., Henzel, W.J., et al., 1995. Cloning, sequencing, and expression of a 24-kDa Ca2qbinding protein activating photoreceptor guanylyl cyclase. J. Biol. Chem. 270, 25200–25206. Ebrey, T., Koutalos, Y., 2001. Vertebrate photoreceptors. Prog. Retin. Eye Res. 20, 49–94. Frings, S., Seifert, R., Godde, M., Kaupp, U.B., 1995. Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels. Neuron 15, 169–179. Gillespie, P.G., Beavo, J.A., 1988. Characterization of a bovine cone photoreceptor phosphodiesterase purified by cyclic GMP–sepharose chromatography. J. Biol. Chem. 263, 8133–8141. Gorczyca, W.A., Polans, A.S., Surgucheva, I.G., Subbaraya, I., Baehr, W., Palczewski, K., 1995. Guanylyl cyclase activating protein. A calcium-sensitive regulator of phototransduction. J. Biol. Chem. 270, 22029–22036. Haeseleer, F., Sokal, I., Li, N., et al., 1999. Molecular characterization of a third member of the guanylyl cyclaseactivating protein subfamily. J. Biol. Chem. 274, 6526–6535. Hamm, H.E., Gilchrist, A., 1996. Heterotrimeric G proteins. Cur. Opin. Cell Biol. 8, 189–196. Hargrave, P.A., McDowell, J.H., 1992. Rhodopsin and phototransduction: a model system for G protein-linked receptors. Int. Rev. Cytol. 137B, 49–97. ´ Harosi, F.I., 1994. An analysis of two spectral properties of vertebrate visual pigments. Vision Res. 34, 1359–1367. Haynes, L.W., Stotz, S.C., 1997. Modulation of rod, but not cone, cGMP-gated photoreceptor channels by calcium– calmodulin. Vis. Neurosci. 14, 233–239. He, W., Cowan, C.W., Wensel, T.G., 1998. RGS9, a GTPase accelerator for phototransduction. Neuron 20, 95–102. Hestrin, S., Korenbrot, J.I., 1990. Activation kinetics of retinal cones and rods: response to intense flashes of light. J. Neurosci. 10, 1967–1973. Hisatomi, O., Iwasa, T., Tokunaga, F., Yasui, A., 1991. Isolation and characterization of a lamprey rhodopsin cDNA. Biochem. Biophys. Res. Commun. 174, 1125–1132. Hisatomi, O., Kayada, S., Aoki, Y., Iwasa, T., Tokunaga, F., 1994. Phylogenetic relationships among vertebrate visual pigments. Vision Res. 34, 3097–3102.

520

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Hisatomi, O., Imanishi, Y., Satoh, T., Tokunaga, F., 1997. Arrestins expressed in killifish photoreceptor cells. FEBS Lett. 411, 12–18. Hisatomi, O., Matsuda, S., Satoh, T., Kotaka, S., Imanishi, Y., Tokunaga, F., 1998. A novel subtype of G-protein-coupled receptor kinase, GRK7, in teleost cone photoreceptors. FEBS Lett. 424, 159–164. Hisatomi, O., Honkawa, H., Imanishi, Y., Satoh, T., Tokunaga, F., 1999. Three kinds of guanylate cyclase expressed in medaka photoreceptor cells in both retina and pineal organ. Biochem. Biophys. Res. Commun. 255, 216–220. Howes, K., Bronson, J.D., Dang, Y.L., et al., 1998. Gene array and expression of mouse retina guanylate cyclase activating proteins 1 and 2. Invest. Ophthalmol. Vis. Sci. 39, 867–875. Hsu, Y.T., Molday, R.S., 1993. Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin. Nature 361, 76–79. Imai, H., Kojima, D., Oura, T., Tachibanaki, S., Terakita, A., Shichida, Y., 1997. Single amino acid residue as a functional determinant of rod and cone visual pigments. Proc. Natl. Acad. Sci. USA 94, 2322–2326. Imanishi, Y., Hisatomi, O., Tokunaga, F., 1999. Two types of arrestins expressed in medaka rod photoreceptors. FEBS Lett. 462, 31–36. Imanishi, Y., Li, N., Sokal, I., et al., 2002. Characterization of retinal guanylate cyclase-activating protein 3 (GCAP3) from zebrafish to man. Eur. J. Neurosci. 15, 63–78. Inglese, J., Glickman, J.F., Lorenz, W., Caron, M.G., Lefkowitz, R.J., 1992a. Isoprenylation of a protein kinase. Requirement of farnesylationya-carboxyl methylation for full enzymatic activity of rhodopsin kinase. J. Biol. Chem. 267, 1422–1425. Inglese, J., Koch, W.J., Caron, M.G., Lefkowitz, R.J., 1992b. Isoprenylation in regulation of signal transduction by Gprotein-coupled receptor kinases. Nature 359, 147–150. Johnson, R.L., Grant, K.B., Zankel, T.C., et al., 1993. Cloning and expression of goldfish opsin sequences. Biochemistry 32, 208–214. Kachi, S., Nishizawa, Y., Olshevskaya, E., et al., 1999. Detailed localization of photoreceptor guanylate cyclase activating protein-1 and -2 in mammalian retinas using light and electron microscopy. Exp. Eye Res. 68, 465–473. Kaupp, U.B., Niidome, T., Tanabe, T., et al., 1989. Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342, 762–766. Kaupp, U.B., Koch, K.-W., 1992. Role of cGMP and Ca2q in vertebrate photoreceptor excitation and adaptation. Annu Rev. Physiol. 54, 153–175. Kawamura, S., 1993. Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by Smodulin. Nature 362, 855–857. Kawamura, S., Murakami, M., 1991. Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods. Nature 349, 420–423. Kawamura, S., Hisatomi, O., Kayada, S., Tokunaga, F., Kuo, C.-H., 1993. Recoverin has S-modulin activity in frog rods. J. Biol. Chem. 268, 14579–14582. Kawamura, S., Kuwata, O., Yamada, M., Matsuda, S., Hisatomi, O., Tokunaga, F., 1996. Photoreceptor protein s26, a cone homologue of S-modulin in frog retina. J. Biol. Chem. 271, 21359–21364.

Kobayashi, Y., Hisatomi, O., Satoh, T., Tokunaga, F., 2001. Identification of phosducins expressed in teleost retinas. FEBS Lett. 502, 117–121. Korenbrot, J.I., Miller, D.L., 1989. Cytoplasmic free calcium concentration in dark-adapted retinal rod outer segments. Vision Res. 29, 939–948. Klenchin, V.A., Calvert, P.D., Bownds, M.D., 1995. Inhibition of rhodopsin kinase by recoverin. Further evidence for a negative feedback system in phototransduction. J. Biol. Chem. 270, 16147–16152. Krylov, D.M., Niemi, G.A., Dizhoor, A.M., Hurley, J.B., 1999. Mapping sites in guanylyl cyclase activating protein-1 required for regulation of photoreceptor membrane guanylyl cyclases. J. Biol. Chem. 274, 10833–10839. Kuhn, H., 1984. Early steps in the light-triggered activation of the cyclic GMP enzymatic pathway in rod photoreceptors. Prog. Retinal Res. 3, 123–156. Kuo, C.H., Akiyama, M., Miki, N., 1989. Isolation of a novel retina-specific clone (MEKA cDNA) encoding a photoreceptor soluble protein. Mol. Brain Res. 6, 1–10. Lamb, T.D., 1995. Photoreceptor spectral sensitivities: common shape in the long-wavelength region. Vision Res. 35, 3083–3091. Laura, R.P., Hurley, J.B., 1998. The kinase homology domain of retinal guanylyl cyclases 1 and 2 specifies the affinity and cooperativity of interaction with guanylyl cyclaseactivating protein-2. Biochemistry 37, 11264–11271. Lee, R.H., Brown, B.M., Lolley, R.N., 1984. Light-induced dephosphorylation of a 33-kDa protein in rod outer segments of rat retina. Biochemistry 23, 1972–1977. Lerea, C.L., Somers, D.E., Hurley, J.B., Klock, I.B., BuntMilam, A.H., 1986. Identification of specific transducin a subunits in retinal rod and cone photoreceptors. Science 234, 77–80. Lerea, C.L., Bunt-Milam, A.H., Hurley, J.B., 1989. A transducin is present in blue-, green-, and red-sensitive cone photoreceptors in the human retina. Neuron 3, 367–376. Liu, X., Seno, K., Nishizawa, Y., et al., 1994. Ultrastructural localization of retinal guanylate cyclase in human and monkey retinas. Exp. Eye Res. 59, 761–768. Lochrie, M.A., Hurley, J.B., Simon, M.I., 1985. Sequence of the a subunit of photoreceptor G protein: homologies between transducin, ras, and elongation factors. Science 228, 96–99. Lowe, D.G., Dizhoor, A.M., Liu, K., et al., 1995. Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2. Proc. Natl. Acad. Sci. USA 92, 5535–5539. Ma, J.-X., Znoiko, S., Othersen, K.L., et al., 2001. A visual pigment expressed in both rod and cone photoreceptors. Neuron 32, 451–461. Matsuda, S., Hisatomi, O., Tokunaga, F., 1999. Role of carboxyl-terminal charges on S-modulin membrane affinity and inhibition of rhodopsin phosphorylation. Biochemistry 38, 1310–1315. Matthews, H.R., Murphy, R.L.W., Fain, G., Lamb, T.D., 1988. Photoreceptor light adaptation is mediated by cytoplasmic calcium concentration. Nature 334, 67–69. Medynski, D.C., Sullivan, K., Smith, D., et al., 1985. Amino acid sequence of the alpha subunit of transducin deduced

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522 from the cDNA sequence. Proc. Natl. Acad. Sci. USA 82, 4311–4315. Mendez, A., Burns, M.E., Sokal, I., et al., 2001. Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proc. Natl. Acad. Sci. USA 98, 9948–9953. Milam, A.H., Dacey, D.M., Dizhoor, A.M., 1993. Recoverin immunoreactivity in mammalian cone bipolar cells. Vis. Neurosci. 10, 1–12. Molday, L.L., Cook, N.J., Kaupp, U.B., Molday, R.S., 1990. The cGMP-gated cation channel of bovine rod photoreceptor cells is associated with a 240-kDa protein exhibiting immunochemical cross-reactivity with spectrin. J. Biol. Chem. 265, 18690–18695. Murakami, A., Yajima, T., Sakuma, H., McLaren, M.J., Inana, G., 1993. X-arrestin: a new retinal arrestin mapping to the X chromosome. FEBS Lett. 334, 203–209. Nakatani, K., Yau, K.-W., 1988. Calcium and light adaptation in retinal rods and cones. Nature 334, 69–71. Nakatani, K., Yau, K.W., 1989. Sodium-dependent calcium extrusion and sensitivity regulation in retinal cones of the salamander. J. Physiol. 409, 525–548. Nathans, J., Hogness, D.S., 1983. Isolation, sequence analysis, and intron–exon arrangement of the gene encoding bovine rhodopsin. Cell 34, 807–814. Nathans, J., Thomas, D., Hogness, D.S., 1986. Molecular genetics of human color vision: the genes encoding blue, green and red pigments. Science 232, 193–202. Nir, I., Ransom, N., 1992. S-antigen in rods and cones of the primate retina: different labeling patterns are revealed with antibodies directed against specific domains in the molecule. J. Histochem. Cytochem. 40, 343–352. Normann, R.A., Werblin, F.S., 1974. Control of retinal sensitivity. I. Light and dark adaptation of vertebrate rods and cones. J. Gen. Physiol. 63, 37–61. Okano, T., Kojima, D., Fukada, Y., Shichida, Y., Yoshizawa, T., 1992. Primary structures of chicken cone visual pigments: vertebrate rhodopsins have evolved out of cone visual pigments. Proc. Natl. Acad. Sci. USA 89, 5932–5936. Ong, O.C., Hu, K., Rong, H., Lee, R.H., Fung, B.K., 1997. Gene structure and chromosome localization of the Ggc subunit of human cone G-protein (GNGT2). Genomics 44, 101–109. Palczewski, K., 1994. Structure and functions of arrestins. Protein Sci. 3, 1355–1361. Palczewski, K., Buczylko, J., Lebioda, L., Crabb, J.W., Polans, A.S., 1993. Identification of the N-terminal region in rhodopsin kinase involved in its interaction with rhodopsin. J. Biol. Chem. 268, 6004–6013. Palczewski, K., Subbaraya, I., Gorczyca, W.A., et al., 1994. Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase-activating protein. Neuron 13, 395–404. Pepe, I.M., 2001. Recent advances in our understanding of rhodopsin and phototransduction. Prog. Retinal Eye Res. 20, 733–759. Picones, A., Korenbrot, J.I., 1995. Permeability and interaction of Ca2q with cGMP-gated ion channels differ in retinal rod and cone photoreceptors. Biophys. J. 69, 120–127. Polans, A.S., Buczylko, J., Crabb, J., Palczewski, K., 1991. A photoreceptor calcium binding protein is recognized by

521

autoantibodies obtained from patients with cancer-associated retinopathy. J. Cell. Biol. 112, 981–989. Polans, A.S., Burton, M.D., Haley, T.L., Crabb, J.W., Palczewski, K., 1993. Recoverin, but not visinin, is an autoantigen in the human retina identified with a cancer-associated retinopathy. Invest. Ophthalmol. Vis. Sci. 34, 81–90. Prinsen, C.F., Szerencsei, R.T., Schnetkamp, P.P., 2000. Molecular cloning and functional expression of the potassiumdependent sodium–calcium exchanger from human and chicken retinal cone photoreceptors. J. Neurosci. 20, 1424–1434. Pugh, E.N., Duda, T., Sitaramayya, A., Sharma, R.K., 1997. Photoreceptor guanylate cyclases: a review. Biosci. Rep. 17, 429–473. Ratto, G.M., Pavne, R., Owen, W.G., Tsien, R.Y., 1988. The concentration of cytosolic free calcium in vertebrate rod outer segments measured with fura-2. J. Neurosci. 8, 3240–3246. Ray, S., Zozulya, S., Niemi, G.A., et al., 1992. Cloning, expression, and crystallization of recoverin, a calcium sensor in vision. Proc. Natl. Acad. Sci. USA 89, 5705–5709. Reilaender, H., Achilles, A., Friedel, U., Maul, G., Lottspeich, F., Cook, N.J., 1992. Primary structure and functional expression of the NayCa, K-exchanger from bovine rod photoreceptors. EMBO J. 11, 1689–1695. Saitou, L., Nei, M., 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406–425. Sakuma, H., Inana, G., Murakami, A., Higashide, T., McLaren, M.J., 1996. Immunolocalization of X-arrestin in human cone photoreceptors. FEBS Lett. 382, 105–110. Seimiya, M., Kusakabe, T., Suzuki, N., 1997. Primary structure and differential gene expression of three membrane forms of guanylyl cyclase found in the eye of the teleost Oryzias latipes. J. Biol. Chem. 272, 23407–23417. Semple-Rowland, S.L., Larkin, P., Bronson, J.D., Nykamp, K., Streit, W.J., Baehr, W., 1999. Characterization of the chicken GCAP gene array and analyses of GCAP1, GCAP2, and GC1 gene expression in normal and rd chicken pineal. Mol. Vis. 5, 14. Seno, K., Kishigami, A., Ihara, S., et al., 1998. A possible role of RGS9 in phototransduction. A bridge between the cGMP-phosphodiesterase system and the guanylyl cyclase system. J. Biol. Chem. 273, 22169–22172. Shyjan, A.W., de-Sauvage, F.J., Gillett, N.A., Goeddel, D.V., Lowe, D.G., 1992. Molecular cloning of a retina-specific membrane guanylyl cyclase. Neuron 9, 727–737. Stryer, L., 1986. Cyclic GMP cascade of vision. Annu. Rev. Neurosci. 9, 87–119. Tachibanaki, S., Tsushima, S., Kawamura, S., 2001. Low amplification and fast visual pigment phosphorylation as mechanisms characterizing cone photoresponses. Proc. Natl. Acad. Sci. USA 98, 14044–14049. Tanaba, T., Nuaba, T., Nukada, Y., et al., 1985. Primary structure of the a-subunit of transducin and its relationship to ras proteins. Nature 315, 242–245. Taniguchi, Y., Hisatomi, O., Yoshida, M., Tokunaga, F., 2001. Pinopsin expressed in retinal photoreceptors of a diurnal gecko. FEBS Lett. 496, 69–74. ´ A., von Veen, T., Farber, D.B., 1994. von Schantz, M., Szel, Expression of phototransduction cascade genes in the ground squirrel retina. Invest. Ophthalmol. Vis. Sci. 35, 3922–3930.

522

O. Hisatomi, F. Tokunaga / Comparative Biochemistry and Physiology Part B 133 (2002) 509–522

Watanabe, Y., Kawasaki, K., Miki, N., Kuo, C.H., 1996. Isolation and analysis of the human MEKA gene encoding a retina-specific protein. Biochem. Biophys. Res. Commun. 170, 951–956. Weiss, E.R., Raman, D., Shirakawa, S., et al., 1998. The cloning of GRK7, a candidate cone opsin kinase, from coneand rod-dominant mammalian retinas. Mol. Vis. 4, 27. Weiss, E.R., Ducceschi, M.H., Horner, T.J., Li, A., Craft, C.M., Osawa, S., 2001. Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction. J. Neurosci. 21, 9175–9184. Wilkins, J.F., Bitensky, M.W., Willardson, B.M., 1996. Regulation of the kinetics of phosducin phosphorylation in retinal rods. J. Biol. Chem. 271, 19232–19237. Willardson, B.M., Wilkins, J.F., Yoshida, T., Bitensky, M.W., 1996. Regulation of phosducin phosphorylation in retinal rods by Ca2q ycalmodulin-dependent adenylyl cyclase. Proc. Natl. Acad. Sci. USA 93, 1475–1479. Wistow, G.J., Katial, A., Craft, C., Shinohara, T., 1986. Sequence analysis of bovine retinal S-antigen. Relationships with a-transducin and G-proteins. FEBS Lett. 196, 23–28.

Yatsunami, K., Khorana, H.G., 1985. GTPase of bovine rod outer segments: the amino acid sequence of the a subunit as derived from the cDNA sequence. Proc. Natl. Acad. Sci. USA 82, 4311–4315. Yau, K.-W., Nakatani, K., 1985. Light-induced reduction of cytoplasmic free calcium in retinal rod outer segment. Nature 313, 579–582. Yokoyama, S., 1995. Amino acid changes and wavelength absorption of visual pigments in vertebrates. Mol. Biol. Evol. 12, 53–61. Yokoyama, S., 2000. Molecular evolution of vertebrate visual pigments. Prog. Retinal Eye Res. 19, 385–419. Yokoyama, R., Yokoyama, S., 1990. Convergent evolution of the red- and green-like visual pigment genes in fish, Astyanax fasciatus, and human. Proc. Natl. Acad. Sci. USA 87, 9315–9318. Zhang, H., Yokoyama, S., 1997. Molecular evolution of the rhodopsin gene of marine lamprey, Petromyzon marinus. Gene 191, 1–6. Zhao, X., Huang, J., Khani, S.C., Palczewski, K., 1998. Molecular forms of human rhodopsin kinase (GRK1). J. Biol. Chem. 273, 5124–5131.