title: Diacylglycerol O-acyltransferase type-1 synthesizes retinyl esters in the retina and retinal pigment epithelium.
abstract: Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1(-/-) mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1(-/-) mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE's) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1(-/-) mice. Further, total retinyl-ester synthase activity was reduced in both dgat1(-/-) retina and RPE.
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Kaylor
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Roxana A
authors.initials: RA
authors.lastname: Radu
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bischoff
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jacob
authors.initials: J
authors.lastname: Makshanoff
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jane
authors.initials: J
authors.lastname: Hu
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Marcia
authors.initials: M
authors.lastname: Lloyd
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Shannan
authors.initials: S
authors.lastname: Eddington
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Tran
authors.initials: T
authors.lastname: Bianconi
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America; Department of Neurobiology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Dean
authors.initials: D
authors.lastname: Bok
authors.affiliation: Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States of America; Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Gabriel H
authors.initials: GH
authors.lastname: Travis
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D051048:Diacylglycerol O-Acyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004952:Esters / Q000378:metabolism; D017353:Gene Deletion; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D012172:Retinaldehyde / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D019745:cis-trans-Isomerases / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
chemical_list: D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D004952:Esters; D010171:Palmitoyl Coenzyme A; D012172:Retinaldehyde; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C056942:lecithin-retinol acyltransferase