| Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. | |
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MedLine Citation:
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PMID: 23143414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Absorption of a light particle by an opsin-pigment causes photoisomerization of its retinaldehyde chromophore. Restoration of light sensitivity to the resulting apo-opsin requires chemical re-isomerization of the photobleached chromophore. This is carried out by a multistep enzyme pathway called the visual cycle. Accumulating evidence suggests the existence of an alternative visual cycle for regenerating opsins in daylight. Here we identified dihydroceramide desaturase-1 (DES1) as a retinol isomerase and an excellent candidate for isomerase-2 in this alternative pathway. DES1 is expressed in retinal Müller cells, where it coimmunoprecipitates with cellular retinaldehyde binding protein (CRALBP). Adenoviral gene therapy with DES1 partially rescued the biochemical and physiological phenotypes in Rpe65(-/-) mice lacking isomerohydrolase (isomerase-1). Knockdown of DES1 expression by RNA interference concordantly reduced isomerase-2 activity in cultured Müller cells. Purified DES1 had very high isomerase-2 activity in the presence of appropriate cofactors, suggesting that DES1 by itself is sufficient for isomerase activity. |
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Authors:
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Joanna J Kaylor; Quan Yuan; Jeremy Cook; Shanta Sarfare; Jacob Makshanoff; Anh Miu; Anita Kim; Paul Kim; Samer Habib; C Nathaniel Roybal; Tongzhou Xu; Steven Nusinowitz; Gabriel H Travis |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-11 |
Journal Detail:
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Title: Nature chemical biology Volume: 9 ISSN: 1552-4469 ISO Abbreviation: Nat. Chem. Biol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2012-12-14 Completed Date: 2013-02-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101231976 Medline TA: Nat Chem Biol Country: United States |
Other Details:
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Languages: eng Pagination: 30-6 Citation Subset: IM |
Affiliation:
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Jules Stein Eye Institute, University of California, Los Angeles School of Medicine, Los Angeles, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chickens Dependovirus / genetics Genetic Therapy Genetic Vectors Isomerases / chemistry, metabolism* Isomerism Mice Mice, Knockout Neuroglia / enzymology* Oxidoreductases / chemistry, metabolism* Retina / enzymology* Vitamin A / metabolism* cis-trans-Isomerases / genetics |
| Grant Support | |
ID/Acronym/Agency:
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R01 EY011713/EY/NEI NIH HHS; R01-EY11713/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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11103-57-4/Vitamin A; EC 1.-/Oxidoreductases; EC 3.1.1.64/retinoid isomerohydrolase; EC 5.-/Isomerases; EC 5.2.-/cis-trans-Isomerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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