Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65
- 5 July 2006
- journal article
- Published by Wiley in FEBS Letters
- Vol. 580 (17) , 4200-4204
- https://doi.org/10.1016/j.febslet.2006.06.078
Abstract
RPE65, a membrane-associated protein in the retinal pigment epithelium, is the isomerohydrolase essential for regenerating 11-cis retinal, the chromophore for visual pigments. RPE65 mutations are associated with inherited retinal dystrophies. Here we report that single point mutations of RPE65, Y144D and P363T, identified in patients with Leber's congenital amaurosis (LCA), significantly decreased the stability of RPE65. Moreover, these mutations altered subcellular localization of RPE65 and abolished its isomerohydrolase activity. These observations suggest that the decreased protein stability and altered subcellular localization of RPE65 may represent a mechanism for these mutations to lead to vision loss in LCA patients.Keywords
This publication has 17 references indexed in Scilit:
- Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycleProceedings of the National Academy of Sciences, 2005
- RPE65 is the isomerohydrolase in the retinoid visual cycleProceedings of the National Academy of Sciences, 2005
- Rpe65 Is the Retinoid Isomerase in Bovine Retinal Pigment EpitheliumCell, 2005
- Dark adaptation and the retinoid cycle of visionProgress in Retinal and Eye Research, 2004
- Retinyl Esters Are the Substrate for IsomerohydrolaseBiochemistry, 2003
- Confronting Complexity: the Interlink of Phototransduction and Retinoid Metabolism in the Vertebrate RetinaProgress in Retinal and Eye Research, 2001
- The Biochemistry of the Visual CycleChemical Reviews, 2001
- How photons start vision.Proceedings of the National Academy of Sciences, 1996
- MOLECULAR MECHANISMS IN VISUAL PIGMENT REGENERATIONPhotochemistry and Photobiology, 1992
- Membrane phospholipids as an energy source in the operation of the visual cycleBiochemistry, 1991