A palmitoylation switch mechanism in the regulation of the visual cycle.
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.
Xue
Linlong
L
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 45 Shattuck Street, Boston, MA 02115, USA.
Gollapalli
Deviprasad R
DR
Maiti
Pranab
P
Jahng
Wan Jin
WJ
Rando
Robert R
RR
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
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