title: Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina.
abstract: 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.
authors.affiliation: Jules Stein Eye Institute, University of California, Los Angeles School of Medicine, Los Angeles, California, USA.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Kaylor
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Jeremy
authors.initials: J
authors.lastname: Cook
authors.forename: Shanta
authors.initials: S
authors.lastname: Sarfare
authors.forename: Jacob
authors.initials: J
authors.lastname: Makshanoff
authors.forename: Anh
authors.initials: A
authors.lastname: Miu
authors.forename: Anita
authors.initials: A
authors.lastname: Kim
authors.forename: Paul
authors.initials: P
authors.lastname: Kim
authors.forename: Samer
authors.initials: S
authors.lastname: Habib
authors.forename: C Nathaniel
authors.initials: CN
authors.lastname: Roybal
authors.forename: Tongzhou
authors.initials: T
authors.lastname: Xu
authors.forename: Steven
authors.initials: S
authors.lastname: Nusinowitz
authors.forename: Gabriel H
authors.initials: GH
authors.lastname: Travis
mesh_terms: D000818:Animals; D002645:Chickens; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism*; D007536:Isomerism; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000201:enzymology*; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D012160:Retina / Q000201:enzymology*; D014801:Vitamin A / Q000378:metabolism*; D019745:cis-trans-Isomerases / Q000235:genetics; D000099178:Retinoid Isomerohydrolase
chemical_list: D007535:Isomerases; D010088:Oxidoreductases; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase