title: Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65.
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.
authors.affiliation: The University of Oklahoma Health Sciences Center, Department of Medicine Endocrinology, Department of Cell Biology, 941 Stanton L. Young Blvd, BSEB 328B, Oklahoma City, OK 73104, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Moiseyev
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D019943:Amino Acid Substitution; D001766:Blindness / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D002460:Cell Line; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D017354:Point Mutation; D021381:Protein Transport / Q000235:genetics; D012172:Retinaldehyde / Q000378:metabolism; D019745:cis-trans-Isomerases / Q000235:genetics / Q000378:metabolism*; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D012172:Retinaldehyde; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase