Confronting Complexity: the Interlink of Phototransduction and Retinoid Metabolism in the Vertebrate Retina

McBee, Joshua K.; Palczewski, Krzysztof; Baehr, Wolfgang; Pepperberg, David R.

doi:10.1016/s1350-9462(01)00002-7

Cited by 332 publications

(320 citation statements)

References 604 publications

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“…Here, we demonstrated that RDH11-14 catalyze hydrogen transfer from the pro-S C 4 position of NADPH but not of NADH. This specificity is also observed in the eye, one of the most active tissues in retinoid metabolism (2,24). For all convergently evolved RDH enzymes from the SDR superfamily, only one conformational orientation of dinucleotides within the binding site has been observed.…”

Section: Dual-substrate Specificity Dual Responsibility; Mechanisticmentioning

confidence: 78%

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Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

Haeseleer¹,

Jang²,

Imanishi³

et al. 2002

Journal of Biological Chemistry

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189

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Retinoids are chromophores involved in vision, transcriptional regulation, and cellular differentiation. Members of the short chain alcohol dehydrogenase/reductase superfamily catalyze the transformation of retinol to retinal. Here, we describe the identification and properties of three enzymes from a novel subfamily of four retinol dehydrogenases (RDH11-14) that display dualsubstrate specificity, uniquely metabolizing all-trans-and cis-retinols with C 15 pro-R specificity. RDH11-14 could be involved in the first step of all-trans-and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). The dualsubstrate specificity of RDH11 explains the minor phenotype associated with mutations in 11-cisretinol dehydrogenase (RDH5) causing fundus albipunctatus in humans and engineered mice lacking RDH5. Furthermore, photoreceptor RDH12 could be involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. These newly identified enzymes add new elements to important retinoid metabolic pathways that have not been explained by previous genetic and biochemical studies.Retinoids are indispensable light-sensitive elements of vision and also serve as essential modulators of cellular differentiation and proliferation in diverse cell types, including those comprising the epithelium and immune system. Retinoids modulate the growth of both normal and malignant cells through their binding to retinoid receptors. All-trans-retinoic acid signals through specific interactions with the nuclear retinoic acid receptors, whereas its isomer, 9-cis-retinoic acid, is a high affinity ligand of retinoic acid receptors and retinoid X receptors. In the retina, light-dependent photoisomerization of 11-cis-retinylidene to the all-transretinylidene moiety of rod and cone photoreceptors is a key reaction that triggers visual * This research was supported by National Institutes of Health Grants EY08061, CA75173, and DK59125, a grant from Research to Prevent Blindness, Inc. (to the Department of Ophthalmology, University of Washington), and by the E. K. Bishop Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. S The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. 1 and 2 and Tables 1-3. § These authors contributed equally to this work. § § Recipient of a Research to Prevent Blindness Senior Investigator Award. To whom correspondence should be addressed: Dept. of Ophthalmology, University of Washington, Seattle,; E-mail: palczews@u.washington.edu. Transformations of retinoids occur mostly through enzymatic or photochemical reactions, although they readily isomerize non-enzymatically to thermodynamic equilibriu...

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Section: Dual-substrate Specificity Dual Responsibility; Mechanisticmentioning

confidence: 78%

“…Restoration of the visual chromophore occurs through a complex set of reactions, termed the retinoid cycle, in photoreceptor cells and adjacent retinal pigment epithelial cells (RPE) 1 (2). Dietary deficiencies in retinoids and retinoid precursors cause visual impairment, developmental abnormalities, and immune deficiency (3,4).…”

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confidence: 99%

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

Haeseleer¹,

Jang²,

Imanishi³

et al. 2002

Journal of Biological Chemistry

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189

227

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“…Upon light absorption, the 11-cis-retinal is photoisomerized to all-trans-retinal, which subsequently activates opsin and triggers the phototransduction cascade (1,2). The 11-cis-retinal chromophore regenerates through a series of reactions of the retinoid visual cycle (3,4).…”

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confidence: 99%

RPE65 from Cone-dominant Chicken Is a More Efficient Isomerohydrolase Compared with That from Rod-dominant Species

Moiseyev

Takahashi

Chen

et al. 2008

Journal of Biological Chemistry

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Cones recover their photosensitivity faster than rods after bleaching. It has been suggested that a higher rate regeneration of 11-cis-retinal, the chromophore for visual pigments, is required for cones to continuously function under bright light conditions. RPE65 is the isomerohydrolase catalyzing a key step in regeneration of 11-cis-retinal. The present study investigated whether RPE65 in a cone-dominant species is more efficient in its enzymatic activity than that from roddominant species. In vitro isomerohydrolase activity assay showed that isomerohydrolase activity in the chicken retinal pigment epithelium (RPE) was 11.7-fold higher than in the bovine RPE, after normalization by RPE65 protein levels. Similar to that of human and bovine, the isomerohydrolase activity in chicken RPE was blocked by two specific inhibitors of lecithin retinal acyltransferase, indicating that chicken RPE65 also uses all-trans-retinyl ester as the direct substrate. To exclude the possibility that the higher isomerohydrolase activity in the chicken RPE could arise from another unknown isomerohydrolase, we expressed chicken and human RPE65 using the adenovirus system in a stable cell line expressing lecithin retinal acyltransferase. Under the same conditions, isomerohydrolase activity of recombinant chicken RPE65 was 7.7-fold higher than that of recombinant human RPE65, after normalization by RPE65 levels. This study demonstrates that RPE65 from the cone-dominant chicken RPE possesses significantly higher specific retinol isomerohydrolase activity, when compared with RPE65 from rod-dominant species, consistent with the faster regeneration rates of visual pigments in cone-dominant retinas.Visual pigments of rods and cones consist of protein opsins and the chromophore, 11-cis-retinal covalently bound to opsins via a Schiff base (1). Upon light absorption, the 11-cis-retinal is photoisomerized to all-trans-retinal, which subsequently activates opsin and triggers the phototransduction cascade (1, 2). The 11-cis-retinal chromophore regenerates through a series of reactions of the retinoid visual cycle (3, 4). The visual cycle has been intensively studied in rod-dominant species such as bovine and mouse. The twocell (photoreceptor and RPE) 2 system of 11-cis-retinal recycling has been proposed for the visual cycle. After reduction of all-trans-retinal by retinol dehydrogenase, the generated all-trans-retinol is transported from the photoreceptor to the RPE and esterified to all-trans-retinyl esters by lecithin retinol acyltransferase (LRAT). The resulting all-trans-retinyl ester can either be stored in the RPE or directly converted to 11-cis-retinol by the isomerohydrolase, which was recently identified as the microsomal protein RPE65 (5-7). RPE65 has been shown to be an essential enzyme in the retinoid visual cycle for 11-cis-retinal regeneration (8). After oxidation of 11-cis-retinol by retinol dehydrogenase-5, the generated 11-cis-retinal is transported back to the photoreceptors to regenerate the visual pigments.It is known that cone...

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“…The vertebrate visual cycle involves two cellular compartments -photoreceptor outer segments and the RPE (retinal pigment epithelium) (Crouch et al, 1996;Lamb and Pugh, 2004;McBee et al, 2001a;McBee et al, 2001b;Rando, 2001;Saari, 2000) (Figure 1). …”

Section: Canonical Retinoid Recycling In Vertebrate Eyesmentioning

confidence: 99%

Parallel visual cycles in the zebrafish retina

Fleisch

2010

Progress in Retinal and Eye Research

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Vertebrate vision necessitates continuous recycling of the chromophore 11-cis retinal (RAL). The classical (or canonical) visual cycle employs a number of enzymes located in the photoreceptor outer segment and RPE (retinal pigment epithelium) of the retina to regenerate 11-cis RAL from all-trans RAL. Cone-dominant species are believed to utilize a second, intra-retinal, pathway for 11-cis RAL generation, involving retinal Müller glia cells. This review summarizes the efforts made in zebrafish to gain a better understanding of the role of these two visual cycles for rod and cone photoreceptor chromophore recycling.

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Confronting Complexity: the Interlink of Phototransduction and Retinoid Metabolism in the Vertebrate Retina

Cited by 332 publications

References 604 publications

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

RPE65 from Cone-dominant Chicken Is a More Efficient Isomerohydrolase Compared with That from Rod-dominant Species

Parallel visual cycles in the zebrafish retina

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