title: A palmitoylation switch mechanism in the regulation of the visual cycle.
abstract: RPE65 is essential for the biosynthesis of 11-cis-retinal, the chromophore of rhodopsin. Here, we show that the membrane-associated form (mRPE65) is triply palmitoylated and is a chaperone for all-trans-retinyl esters, allowing their entry into the visual cycle for processing into 11-cis-retinal. The soluble form of RPE65 (sRPE65) is not palmitoylated and is a chaperone for vitamin A, rather than all-trans-retinyl esters. Thus, the palmitoylation of RPE65 controls its ligand binding selectivity. The two chaperones are interconverted by lecithin retinol acyl transferase (LRAT) acting as a molecular switch. Here mRPE65 is a palmitoyl donor, revealing a new acyl carrier protein role for palmitoylated proteins. When chromophore synthesis is not required, mRPE65 is converted into sRPE65 by LRAT, and further chromophore synthesis is blocked. The studies reveal new roles for palmitoylated proteins as molecular switches and LRAT as a palmitoyl transferase whose role is to catalyze the mRPE65 to sRPE65 conversion.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 45 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Linlong
authors.initials: L
authors.lastname: Xue
authors.forename: Deviprasad R
authors.initials: DR
authors.lastname: Gollapalli
authors.forename: Pranab
authors.initials: P
authors.lastname: Maiti
authors.forename: Wan Jin
authors.initials: WJ
authors.lastname: Jahng
authors.forename: Robert R
authors.initials: RR
authors.lastname: Rando
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D005136:Eye Proteins; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D008024:Ligands; D018832:Molecular Chaperones / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012172:Retinaldehyde / Q000096:biosynthesis*; D012243:Rhodopsin / Q000096:biosynthesis; D014212:Tretinoin / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*; D014801:Vitamin A / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D005229:Fatty Acids, Monounsaturated; D008024:Ligands; D018832:Molecular Chaperones; D020033:Protein Isoforms; D011506:Proteins; D014801:Vitamin A; C008757:palmitoleic acid; D014212:Tretinoin; D012243:Rhodopsin; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D012172:Retinaldehyde