Identification of DES1 as a Vitamin A Isomerase in Müller Glial Cells of the Retina
| Autor: | Joanna J. Kaylor, Shanta Sarfare, C Nathaniel Roybal, Paul Kim, Tongzhou Xu, Samer Habib, Gabriel H. Travis, Steven Nusinowitz, Jeremy D. Cook, Anita Kim, Anh Miu, Quan Yuan, Jacob Makshanoff |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
cis-trans-Isomerases
Opsin Biochemistry & Molecular Biology Isomerase activity genetic structures Knockout Genetic Vectors Biology Article Retina 03 medical and health sciences Medicinal and Biomolecular Chemistry Mice 0302 clinical medicine Isomerism Animals Isomerases Vitamin A Molecular Biology 030304 developmental biology Mice Knockout 0303 health sciences Gene knockdown Retinol isomerase Cell Biology Genetic Therapy Dependovirus RPE65 Biochemistry Cis-trans-Isomerases Retinaldehyde sense organs Biochemistry and Cell Biology Oxidoreductases Chickens Neuroglia 030217 neurology & neurosurgery Visual phototransduction |
| Zdroj: | Nature chemical biology Nature chemical biology, vol 9, iss 1 |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | 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 alternate 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 alternate pathway. DES1 is expressed in retinal Müller cells where it co-immunoprecipitates 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 possessed very high isomerase-2 activity in the presence of appropriate cofactors, suggesting that DES1 by itself is sufficient for isomerase activity. |
| Databáze: | OpenAIRE |
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