retinaldehyde

Summary

Summary: A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in "dark" reactions to return to the native trans-configuration.

Top Publications

  1. Weng J, Mata N, Azarian S, Tzekov R, Birch D, Travis G. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell. 1999;98:13-23 pubmed
    ..Mice lacking RmP show delayed dark adaptation, increased all-trans-retinaldehyde (all-trans-RAL) following light exposure, elevated phosphatidylethanolamine (PE) in outer segments, ..
  2. Masutomi K, Chen C, Nakatani K, Koutalos Y. All-trans retinal mediates light-induced oxidation in single living rod photoreceptors. Photochem Photobiol. 2012;88:1356-61 pubmed publisher
    ..Its removal through reduction to all-trans retinol protects photoreceptor outer segments against light-induced oxidative damage. ..
  3. Sexton T, Golczak M, Palczewski K, Van Gelder R. Melanopsin is highly resistant to light and chemical bleaching in vivo. J Biol Chem. 2012;287:20888-97 pubmed publisher
    ..The data support a model in which retinal is continuously covalently bound to melanopsin and may function through a reversible, bistable mechanism. ..
  4. Desvergne B. Retinaldehyde: more than meets the eye. Nat Med. 2007;13:671-3 pubmed
  5. Saari J. Vitamin A metabolism in rod and cone visual cycles. Annu Rev Nutr. 2012;32:125-45 pubmed publisher
    ..Recent progress in the characterization of rod and cone visual cycle components and reactions will result in the development of approaches to the amelioration of blinding eye diseases associated with visual cycle defects. ..
  6. Estevez M, Ala Laurila P, Crouch R, Cornwall M. Turning cones off: the role of the 9-methyl group of retinal in red cones. J Gen Physiol. 2006;128:671-85 pubmed
    ..In red cones, the interaction of the 9-methyl group of retinal with opsin promotes efficient Meta II decay and, thus, the rapid rate of recovery. ..
  7. Palczewski K. Chemistry and biology of vision. J Biol Chem. 2012;287:1612-9 pubmed publisher
    ..Moreover, other nonconventional retinal opsins such as the circadian rhythm regulator melanopsin also initiate light-activated signaling based on similar photochemistry...
  8. Chen G, Zhang Y, Lu D, Li N, Ross A. Retinoids synergize with insulin to induce hepatic Gck expression. Biochem J. 2009;419:645-53 pubmed publisher
    ..Understanding the underlying mechanism that mediates the synergy may be helpful for developing a treatment strategy for patients with diabetes...
  9. Wang T, Duan Y. Chromophore channeling in the G-protein coupled receptor rhodopsin. J Am Chem Soc. 2007;129:6970-1 pubmed

More Information

Publications71

  1. Nawrot M, Liu T, Garwin G, Crabb J, Saari J. Scaffold proteins and the regeneration of visual pigments. Photochem Photobiol. 2006;82:1482-8 pubmed
    CRALBP, cellular retinaldehyde-binding protein, is a retinoid-binding protein necessary for efficient regeneration of rod and cone visual pigments...
  2. Radu R, Hu J, Peng J, Bok D, Mata N, Travis G. Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells. J Biol Chem. 2008;283:19730-8 pubmed publisher
    ..perception begins with the absorption of a photon by an opsin pigment, inducing isomerization of its 11-cis-retinaldehyde chromophore...
  3. 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;107:22084-9 pubmed publisher
    ..Because cOpn5m is the only UV-sensitive opsin among the opsins found so far in chicken, this study provides the molecular basis for UV reception in chicken...
  4. Calikoglu E, Sorg O, Tran C, Grand D, Carraux P, Saurat J, et al. UVA and UVB decrease the expression of CD44 and hyaluronate in mouse epidermis, which is counteracted by topical retinoids. Photochem Photobiol. 2006;82:1342-7 pubmed
    ..increase the expression of CD44, hyaluronate and hyaluronate synthase (HAS)s in mouse epidermis; (3) topical retinaldehyde restores the epidermal thickness and CD44 expression which are correlated with clinical improvement in lichen ..
  5. Collard F, Vertommen D, Fortpied J, Duester G, van Schaftingen E. Identification of 3-deoxyglucosone dehydrogenase as aldehyde dehydrogenase 1A1 (retinaldehyde dehydrogenase 1). Biochimie. 2007;89:369-73 pubmed
    ..that it corresponded to aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme known to catalyze the oxidation of retinaldehyde to retinoic acid...
  6. Miyagishima K, Cornwall M, Sampath A. Metabolic constraints on the recovery of sensitivity after visual pigment bleaching in retinal rods. J Gen Physiol. 2009;134:165-75 pubmed publisher
    ..These results indicate the inner segment is the primary source of reducing equivalents after pigment bleaching, with the reduction of all-trans retinal to all-trans retinol playing a key step in the recovery of sensitivity...
  7. Ala Laurila P, Donner K, Crouch R, Cornwall M. Chromophore switch from 11-cis-dehydroretinal (A2) to 11-cis-retinal (A1) decreases dark noise in salamander red rods. J Physiol. 2007;585:57-74 pubmed
  8. Dalfo D, Marqués N, Albalat R. Analysis of the NADH-dependent retinaldehyde reductase activity of amphioxus retinol dehydrogenase enzymes enhances our understanding of the evolution of the retinol dehydrogenase family. FEBS J. 2007;274:3739-3752 pubmed publisher
    ..dehydrogenase 1 and retinol dehydrogenase 2 are microsomal proteins that catalyze the reduction of all-trans-retinaldehyde using NADH as cofactor, a remarkable combination of substrate and cofactor preferences...
  9. Alsop D, Brown S, Van der Kraak G. The effects of copper and benzo[a]pyrene on retinoids and reproduction in zebrafish. Aquat Toxicol. 2007;82:281-95 pubmed
    ..Specifically that dietary retinoids appear to support normal reproduction in the absence of internal retinoid stores...
  10. Standfuss J, Edwards P, D ANTONA A, Fransen M, Xie G, Oprian D, et al. The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature. 2011;471:656-60 pubmed publisher
    ..We thus show how an agonist ligand can activate its GPCR...
  11. KANE M, Folias A, Napoli J. HPLC/UV quantitation of retinal, retinol, and retinyl esters in serum and tissues. Anal Biochem. 2008;378:71-9 pubmed publisher
    ..The assays described here provide for sensitive and rigorous quantification of endogenous RE, ROL, and RAL to elucidate retinoid homeostasis in disease states such as Alzheimer's disease, type 2 diabetes, obesity, and cancer...
  12. Ahmad S, Joyce M, Boggess B, O Tousa J. The role of Drosophila ninaG oxidoreductase in visual pigment chromophore biogenesis. J Biol Chem. 2006;281:9205-9 pubmed
    ..These data are used to review chromophore biosynthesis and propose that NinaG acts in the conversion of (3R)-3-hydroxyretinol to the 3S enantiomer...
  13. Piechnick R, Heck M, Sommer M. Alkylated hydroxylamine derivatives eliminate peripheral retinylidene Schiff bases but cannot enter the retinal binding pocket of light-activated rhodopsin. Biochemistry. 2011;50:7168-76 pubmed publisher
    ..Furthermore, the use of alkylated hydroxylamines should not be limited to in vitro studies and could help elucidate visual signal transduction mechanisms in the living cells of the retina...
  14. Gao S, Maeda T, Okano K, Palczewski K. A microparticle/hydrogel combination drug-delivery system for sustained release of retinoids. Invest Ophthalmol Vis Sci. 2012;53:6314-23 pubmed
  15. Sparrow J, Wu Y, Kim C, Zhou J. Phospholipid meets all-trans-retinal: the making of RPE bisretinoids. J Lipid Res. 2010;51:247-61 pubmed publisher
    ..The propensity of these compounds to negatively impact on the cells has been linked to the pathogenesis of some retinal disorders including juvenile onset recessive Stargardt disease and age-related macular degeneration...
  16. Choe H, Kim Y, Park J, Morizumi T, Pai E, Krauss N, et al. Crystal structure of metarhodopsin II. Nature. 2011;471:651-5 pubmed publisher
    ..By comparison with early photoproducts we propose how retinal translocation and rotation induce the gross conformational changes characteristic for Meta?II. The structures can now serve as models for the large GPCR family...
  17. Kono M, Crouch R. In vitro assays of rod and cone opsin activity: retinoid analogs as agonists and inverse agonists. Methods Mol Biol. 2010;652:85-94 pubmed publisher
    ..The understanding of the effects of ligands on cone opsin activity can potentially be applied to future therapeutic agents targeting opsins...
  18. Maeda A, Maeda T, Golczak M, Palczewski K. Retinopathy in mice induced by disrupted all-trans-retinal clearance. J Biol Chem. 2008;283:26684-93 pubmed publisher
    ..These findings provide direct evidence that aberrant production of toxic condensation byproducts of the visual cycle in mice can lead to rapid, progressive retinal degeneration...
  19. Sato K, Ozaki T, Ishiguro S, Nakazawa M. M-opsin protein degradation is inhibited by MG-132 in Rpe65?/? retinal explant culture. Mol Vis. 2012;18:1516-25 pubmed
    ..We used an explant culture system to evaluate whether posttranslational downregulation of M-opsin protein in Rpe65(-/-) mice is caused by proteolytic degradation...
  20. Ziouzenkova O, Orasanu G, Sharlach M, Akiyama T, Berger J, Viereck J, et al. Retinaldehyde represses adipogenesis and diet-induced obesity. Nat Med. 2007;13:695-702 pubmed
    ..Retinoic acid is formed solely from retinaldehyde (Rald), which in turn is derived from vitamin A. Rald currently has no defined biologic role outside the eye...
  21. Sakmar T. Timing is everything: Direct measurement of retinol production in cones and rods. J Gen Physiol. 2006;128:147-8 pubmed
  22. Kojima D, Mori S, Torii M, Wada A, Morishita R, Fukada Y. UV-sensitive photoreceptor protein OPN5 in humans and mice. PLoS ONE. 2011;6:e26388 pubmed publisher
    ..These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues...
  23. Samardzija M, Tanimoto N, Kostic C, Beck S, Oberhauser V, Joly S, et al. In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death. Hum Mol Genet. 2009;18:1266-75 pubmed publisher
    ..These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods...
  24. Sommer M, Smith W, Farrens D. Dynamics of arrestin-rhodopsin interactions: acidic phospholipids enable binding of arrestin to purified rhodopsin in detergent. J Biol Chem. 2006;281:9407-17 pubmed
    ..We anticipate that this new ability to study these proteins in a defined, purified system will facilitate further structural and dynamic studies of arrestin-rhodopsin interactions...
  25. Maeda A, Golczak M, Chen Y, Okano K, Kohno H, Shiose S, et al. Primary amines protect against retinal degeneration in mouse models of retinopathies. Nat Chem Biol. 2011;8:170-8 pubmed publisher
  26. Kono M, Crouch R. Probing human red cone opsin activity with retinal analogues. J Nat Prod. 2011;74:391-4 pubmed publisher
    ..These results suggest that the red cone opsin has a more open structure in the chromophore binding region than rhodopsin and its activation or deactivation as a G-protein receptor may be less selective than rhodopsin...
  27. Brown M, Heyn M, Job C, Kim S, Moltke S, Nakanishi K, et al. Solid-state 2H NMR spectroscopy of retinal proteins in aligned membranes. Biochim Biophys Acta. 2007;1768:2979-3000 pubmed
    ..Torsional strain is relaxed in the meta I state that precedes subsequent receptor activation. Comparison of the two retinal proteins using solid-state 2H NMR is thus illuminating in terms of their different biological functions...
  28. Noorwez S, Sama R, Kaushal S. Calnexin improves the folding efficiency of mutant rhodopsin in the presence of pharmacological chaperone 11-cis-retinal. J Biol Chem. 2009;284:33333-42 pubmed publisher
    ..These results demonstrate that misfolded rather than correctly folded rhodopsin is a substrate for Cnx and that the interaction between Cnx and mutant, misfolded rhodopsin, can be targeted to increase the yield of folded mutant protein...
  29. Barnes L, Tran C, Sorg O, Hotz R, Grand D, Carraux P, et al. Synergistic effect of hyaluronate fragments in retinaldehyde-induced skin hyperplasia which is a Cd44-dependent phenomenon. PLoS ONE. 2010;5:e14372 pubmed publisher
    ..We have recently shown that intermediate size HA fragments (HAFi) reverse skin atrophy by a CD44-dependent mechanism...
  30. Boyer N, Higbee D, Currin M, Blakeley L, Chen C, Ablonczy Z, et al. Lipofuscin and N-retinylidene-N-retinylethanolamine (A2E) accumulate in retinal pigment epithelium in absence of light exposure: their origin is 11-cis-retinal. J Biol Chem. 2012;287:22276-86 pubmed publisher
    ..The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane...
  31. Billings S, Pierzchalski K, Butler Tjaden N, Pang X, Trainor P, KANE M, et al. The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development. FASEB J. 2013;27:4877-89 pubmed publisher
    Oxidation of retinol via retinaldehyde results in the formation of the essential morphogen all-trans-retinoic acid (ATRA)...
  32. Vogel R, Ludeke S, Siebert F, Sakmar T, Hirshfeld A, Sheves M. Agonists and partial agonists of rhodopsin: retinal polyene methylation affects receptor activation. Biochemistry. 2006;45:1640-52 pubmed
    ..The 9-methyl group appears therefore essential for the correct positioning of retinal to link protonation of the cytoplasmic motif with protonation of Glu 113 during receptor activation...
  33. Ala Laurila P, Kolesnikov A, Crouch R, Tsina E, Shukolyukov S, Govardovskii V, et al. Visual cycle: Dependence of retinol production and removal on photoproduct decay and cell morphology. J Gen Physiol. 2006;128:153-69 pubmed
    ..The more rapid rates of retinol production in cones compared to rods are consistent with the more rapid operation of the visual cycle in these cells...
  34. Voolstra O, Oberhauser V, Sumser E, Meyer N, Maguire M, Huber A, et al. NinaB is essential for Drosophila vision but induces retinal degeneration in opsin-deficient photoreceptors. J Biol Chem. 2010;285:2130-9 pubmed publisher
    ..Thus, our study identifies NinaB as a key component for visual pigment production and provides evidence that chromophore in opsin-deficient photoreceptors can elicit retinal degeneration...
  35. Imasheva E, Balashov S, Choi A, Jung K, Lanyi J. Reconstitution of Gloeobacter violaceus rhodopsin with a light-harvesting carotenoid antenna. Biochemistry. 2009;48:10948-55 pubmed publisher
  36. Gallego O, Ruiz F, Ardèvol A, Dominguez M, Alvarez R, de Lera A, et al. Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10. Proc Natl Acad Sci U S A. 2007;104:20764-9 pubmed
    ..In vitro, AKR1B10 exhibits a much higher retinaldehyde reductase activity than any other human AKR, including AKR1B1 (aldose reductase)...
  37. Zhang H, Fan J, Li S, Karan S, Rohrer B, Palczewski K, et al. Trafficking of membrane-associated proteins to cone photoreceptor outer segments requires the chromophore 11-cis-retinal. J Neurosci. 2008;28:4008-14 pubmed publisher
    ..Furthermore, the presence of 11-cis-retinal is essential for proper transport of several membrane-associated cone phototransduction polypeptides in these cones...
  38. Maeda A, Maeda T, Golczak M, Chou S, Desai A, Hoppel C, et al. Involvement of all-trans-retinal in acute light-induced retinopathy of mice. J Biol Chem. 2009;284:15173-83 pubmed publisher
    ..These findings further understanding of the mechanisms involved in light-induced retinal degeneration...
  39. Irie T, Sugimoto T, Ueki N, Senoo H, Seki T. Retinoid storage in the egg of reptiles and birds. Comp Biochem Physiol B Biochem Mol Biol. 2010;157:113-8 pubmed publisher
  40. Maeda T, Dong Z, Jin H, Sawada O, Gao S, Utkhede D, et al. QLT091001, a 9-cis-retinal analog, is well-tolerated by retinas of mice with impaired visual cycles. Invest Ophthalmol Vis Sci. 2013;54:455-66 pubmed publisher
  41. Rózanowska M, Handzel K, Boulton M, Rozanowski B. Cytotoxicity of all-trans-retinal increases upon photodegradation. Photochem Photobiol. 2012;88:1362-72 pubmed publisher
    ..In conclusion, photodegradation products of AtRal may impose a significant threat to the retina and therefore their roles in retinal pathology need to be explored...
  42. Balashov S, Imasheva E, Wang J, Lanyi J. Excitation energy-transfer and the relative orientation of retinal and carotenoid in xanthorhodopsin. Biophys J. 2008;95:2402-14 pubmed publisher
    ..The results establish xanthorhodopsin as the simplest biological excited-state donor-acceptor system for collecting light...
  43. Chen M, Kuemmel C, Birge R, Knox B. Rapid release of retinal from a cone visual pigment following photoactivation. Biochemistry. 2012;51:4117-25 pubmed publisher
  44. Chen Y, Okano K, Maeda T, Chauhan V, Golczak M, Maeda A, et al. Mechanism of all-trans-retinal toxicity with implications for stargardt disease and age-related macular degeneration. J Biol Chem. 2012;287:5059-69 pubmed publisher
    ..A similar mechanism may be operative in human Stargardt disease and age-related macular degeneration...
  45. Oberhauser V, Voolstra O, Bangert A, von Lintig J, Vogt K. NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide. Proc Natl Acad Sci U S A. 2008;105:19000-5 pubmed publisher
    ..Our study demonstrates that trans/cis isomerase activity can be intrinsic to this class of proteins and establishes these enzymes as key components for both invertebrate and vertebrate vision...
  46. Rhinn M, Schuhbaur B, Niederreither K, Dolle P. Involvement of retinol dehydrogenase 10 in embryonic patterning and rescue of its loss of function by maternal retinaldehyde treatment. Proc Natl Acad Sci U S A. 2011;108:16687-92 pubmed publisher
    ..Morphogenetic RA gradients are thought to be set up by tissue-specific actions of retinaldehyde dehydrogenases (RALDHs) and catabolizing enzymes...
  47. Kunchithapautham K, Coughlin B, Crouch R, Rohrer B. Cone outer segment morphology and cone function in the Rpe65-/- Nrl-/- mouse retina are amenable to retinoid replacement. Invest Ophthalmol Vis Sci. 2009;50:4858-64 pubmed publisher
    ..Here, we determine the consequences of 11-cis retinal withdrawal and supplementation on cone development in the all-cone Nrl(-/-) retina...
  48. Yamamoto K, Yoon K, Ueda K, Hashimoto M, Sparrow J. A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine. Invest Ophthalmol Vis Sci. 2011;52:9084-90 pubmed publisher
    ..The formation of bisretinoid is accentuated in some forms of retinal degeneration. The detection of a novel bisretinoid fluorophore that is a conjugate of all-trans-retinal and glycerophosphoethanolamine is reported...
  49. Park J, Scheerer P, Hofmann K, Choe H, Ernst O. Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature. 2008;454:183-7 pubmed publisher
    ..The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation...
  50. Maeda T, Cideciyan A, Maeda A, Golczak M, Aleman T, Jacobson S, et al. Loss of cone photoreceptors caused by chromophore depletion is partially prevented by the artificial chromophore pro-drug, 9-cis-retinyl acetate. Hum Mol Genet. 2009;18:2277-87 pubmed publisher
    ..These results suggest that chronic lack of chromophore leads to progressive loss of cones in mice and humans. Therapy for LCA patients should be geared toward early adequate delivery of chromophore to cone photoreceptors...
  51. Saari J, Nawrot M, Stenkamp R, Teller D, Garwin G. Release of 11-cis-retinal from cellular retinaldehyde-binding protein by acidic lipids. Mol Vis. 2009;15:844-54 pubmed
    To determine molecular mechanisms for the release of 11-cis-retinal from the binding pocket of cellular retinaldehyde-binding protein (CRALBP).
  52. Li R, Chen W, Li Y, Zhang Y, Chen G. Retinoids synergized with insulin to induce Srebp-1c expression and activated its promoter via the two liver X receptor binding sites that mediate insulin action. Biochem Biophys Res Commun. 2011;406:268-72 pubmed publisher
    ..The RA- and insulin-induced Srebp-1c expression converged at the same sites in its promoter, indicating the roles of vitamin A in regulation of hepatic gene expression...
  53. Bandyopadhyay M, Rohrer B. Photoreceptor structure and function is maintained in organotypic cultures of mouse retinas. Mol Vis. 2010;16:1178-85 pubmed
    ..Here, we further examined rod and cone development, chromophore production by the RPE, and photoreceptor signaling to the inner retina under organ culture conditions...
  54. Palczewski K. Retinoids for treatment of retinal diseases. Trends Pharmacol Sci. 2010;31:284-95 pubmed publisher
  55. Luecke H, Schobert B, Stagno J, Imasheva E, Wang J, Balashov S, et al. Crystallographic structure of xanthorhodopsin, the light-driven proton pump with a dual chromophore. Proc Natl Acad Sci U S A. 2008;105:16561-5 pubmed publisher
  56. Scheerer P, Park J, Hildebrand P, Kim Y, Krauss N, Choe H, et al. Crystal structure of opsin in its G-protein-interacting conformation. Nature. 2008;455:497-502 pubmed publisher
    ..On the basis of the Ops*-GalphaCT structure and known conformational changes in Galpha, we discuss signal transfer from the receptor to the G protein nucleotide-binding site...
  57. Fan J, Rohrer B, Frederick J, Baehr W, Crouch R. Rpe65-/- and Lrat-/- mice: comparable models of leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2008;49:2384-9 pubmed publisher
  58. Kanan Y, Moiseyev G, Agarwal N, Ma J, Al Ubaidi M. Light induces programmed cell death by activating multiple independent proteases in a cone photoreceptor cell line. Invest Ophthalmol Vis Sci. 2007;48:40-51 pubmed
    ..The objective of this study was to determine the molecular events leading to the death of photoreceptor cells...
  59. Gearhart P, Gearhart C, Thompson D, Petersen Jones S. Improvement of visual performance with intravitreal administration of 9-cis-retinal in Rpe65-mutant dogs. Arch Ophthalmol. 2010;128:1442-8 pubmed publisher
    ..To determine the efficacy of intravitreal administration of 9-cis-retinal in restoring visual function in Rpe65-mutant dogs...