Preservation of light signaling to the suprachiasmatic nucleus in vitamin A-deficient mice

Thompson, Carol L.; Blaner, William S.; Gelder, Russell N. Van; Lai, Katherine; Quadro, Loredana; Colantuoni, Vittorio; Gottesman, Max E.; Sancar, Aziz

doi:10.1073/pnas.201301498

Cited by 64 publications

(59 citation statements)

References 50 publications

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“…Either melanopsin can utilize a chromophore that does not require LRAT activity (albeit with reduced function), or another photopigment is capable of mediating PLR function in the presence of melanopsin apoprotein. Interestingly, another inner retina-mediated process, namely retinohypothalamic signaling to the suprachiasmatic nucleus, important for circadian rhythm entrainment, is preserved in the face of near total vitamin A depletion (54).…”

Section: Discussionmentioning

confidence: 99%

Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Batten

Imanishi

Maeda

et al. 2004

Journal of Biological Chemistry

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331

380

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Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat؊/؊) mouse. Despite the expression of LRAT in multiple tissues, the Lrat؊/؊ mouse develops normally. The histological analysis and electron microscopy of the retina for 6 -8-week-old Lrat؊/؊ mice revealed that the rod outer segments are ϳ35% shorter than those of Lrat؉/؉ mice, whereas other neuronal layers appear normal. Lrat؊/؊ mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat؊/؊ mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.Lecithin-retinol acyltransferase (LRAT) 1 converts all-transretinol (vitamin A) to all-trans-retinyl esters in several tissues, including the liver, lung, pancreas, intestine, testis, and the retinal pigmented epithelium (RPE) (1-5). LRAT activity in the RPE has been studied for more than 60 years (6), but the enzyme was only recently identified on the molecular level as a 25-kDa integral membrane protein (7). All-trans-retinyl esters are intermediate compounds in a metabolic pathway ("visual cycle" or "retinoid cycle") that recycles 11-cis-retinal, the chromophore of rhodopsin and cone pigments (for review, see Refs. 8 -10). In this cycle, all-trans-retinal dissociates from rhodopsin and cone pigments after photobleaching. In the photoreceptors, all-trans-retinal is reduced to all-trans-retinol and subsequently exported to the adjacent RPE. In the RPE, alltrans-retinol is esterified by LRAT and stored. All-trans-retinyl esters have been suggested to be the substrate for a putative isomerohydrolase in the RPE (11) and for a retinyl ester hydrolase that produces all-trans-retinol, a substrate for the putative isomerase (for review, see Ref. 12). Ultimately, 11-cisretinol is produced, oxidized to 11-cis-retinal, and exported to the photoreceptors. In the rod and cone photoreceptor outer segments, 11-cis-retinal recombines with opsins to form rhodopsin and cone pigments (for review, see Ref. 8).Human LRAT cDNA was cloned from a retinal-RPE cDNA library (7) and rodent Lrat cDNA from liver and other tissues (13-15). Lrat mRNA was shown to be a 5.0-kb species expressed in the RPE, and the multiple transcripts based on differential polyadenylation were detected in several other tissues known for the highest LRAT activity (13). The human LRAT polypeptide consisted of 230 ...

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Section: Discussionmentioning

confidence: 99%

Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Batten

Imanishi

Maeda

et al. 2004

Journal of Biological Chemistry

Self Cite

331

380

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“…There is, however, one additional argument in favor of mCrys being involved in the light induction of mPer1. Retinal-depleted micewhich should be devoid of functional opsins-show normal mPer1 and mPer2 induction in the SCN, suggesting the existence of nonopsin photoreceptors in the eye (Thompson et al, 2001). Yet it is still possible that residual retinal leads to some functional opsins in these mice, which is also suggested by the normal mPer2 induction in the retinal-depleted mice.…”

Section: Brdm1mentioning

confidence: 99%

Genetic analysis of the circadian system in Drosophila melanogaster and mammals

2002

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ABSTRACT:The fruit fly, Drosophila melanogaster, has been a grateful object for circadian rhythm researchers over several decades. Behavioral, genetic, and molecular studies helped to reveal the genetic bases of circadian time keeping and rhythmic behaviors. Contrary, mammalian rhythm research until recently was mainly restricted to descriptive and physiologic approaches. As in many other areas of research, the surprising similarity of basic biologic principles between the little fly and our own species, boosted the progress of unraveling the genetic foundation of mammalian clock mechanisms. Once more, not only the basic mechanisms, but also the molecules involved in establishing our circadian system are taken or adapted from the fly. This review will try to give a comparative overview about the two systems, highlighting similarities as well as specifics of both insect and murine clocks.

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“…Although rhodopsins also contribute to Drosophila circadian photoreception (HelfrichForster et al 2001), a major circadian photoreceptor in this organism was shown to be a cryptochrome, with flavin adenin dinucleotide (FAD) and methenyltetrahydrofolate (MTHF) as chromophores Stanewsky et al 1998). Mammalian cryptochromes may also be circadian photoreceptors (Selby et al 2000;Thompson et al 2001), although the evidence is stronger that they are important central clock components (Kume et al 1999;van der Horst et al 1999). Cryptochromes are closely related to photolyases (blue light-activated DNA repair enzymes), which led to the idea that the DNA binding property of photolyases was retained in cryptochromes (Cashmore et al 1999;Emery et al 1998).…”

Section: Introductionmentioning

confidence: 99%

The Coevolution of Blue-Light Photoreception and Circadian Rhythms

Gehring

Rosbash

2003

Journal of Molecular Evolution

112

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Abstract. Sunlight is a primary source of energy for life. However, its UV component causes DNA damage. We suggest that the strong UV component of sunlight contributed to the selective pressure for the evolution of the specialized photoreceptor cryptochrome from photolyases involved in DNA repair and propose that early metazoans avoided irradiation by descending in the oceans during the daytime. We suggest further that it is not coincidental that bluelight photoreception evolved in an aquatic environment, since only blue light can penetrate to substantial depths in water. These photoreceptors were then also critical for sensing the decreased luminescence that signals the coming of night and the time to return to the surface. The oceans and the 24-h lightdark cycle therefore provided an optimal setting for an early evolutionary relationship between blue-light photoreception and circadian rhythmicity.

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Preservation of light signaling to the suprachiasmatic nucleus in vitamin A-deficient mice

Cited by 64 publications

References 50 publications

Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Genetic analysis of the circadian system in Drosophila melanogaster and mammals

The Coevolution of Blue-Light Photoreception and Circadian Rhythms

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