ArticleProceedings of the National Academy of Sciences of the United States of America2014
Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy.Biomolecules · 2025Review
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Neural and Müller glial adaptation of the retina to photoreceptor degeneration.Neural regeneration research · 2023Review
- Destabilizing COXIV in Müller Glia Increases Retinal Glycolysis and Alters Scotopic Electroretinogram.Cells · 2022Article
- Acyl-CoA:wax alcohol acyltransferase 2 modulates the cone visual cycle in mouse retina.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Non-visual Opsins and Novel Photo-Detectors in the Vertebrate Inner Retina Mediate Light Responses Within the Blue Spectrum Region.Cellular and molecular neurobiology · 2022Review
- Müller glial responses compensate for degenerating photoreceptors in retinitis pigmentosa.Experimental & molecular medicine · 2021Article
- Function of mammalian M-cones depends on the level of CRALBP in Müller cells.The Journal of general physiology · 2021Article
- Molecular components affecting ocular carotenoid and retinoid homeostasis.Progress in retinal and eye research · 2021Review
- Transduction and Adaptation Mechanisms in the Cilium or Microvilli of Photoreceptors and Olfactory Receptors From Insects to Humans.Frontiers in cellular neuroscience · 2021Review
- Deficiency in Acyl-CoA:Wax Alcohol Acyltransferase 2 causes evaporative dry eye disease by abolishing biosynthesis of wax esters.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Retina Organoid Transplants Develop Photoreceptors and Improve Visual Function in RCS Rats With RPE Dysfunction.Investigative ophthalmology & visual science · 2020Article
- Shedding new light on the generation of the visual chromophore.Proceedings of the National Academy of Sciences of the United States of America · 2020Review
- Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells.Neuron · 2019Article
- Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Peropsin modulates transit of vitamin A from retina to retinal pigment epithelium.The Journal of biological chemistry · 2017Article
- The role of retinol dehydrogenase 10 in the cone visual cycle.Scientific reports · 2017Article
- Blue light regenerates functional visual pigments in mammals through a retinyl-phospholipid intermediate.Nature communications · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.
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