Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65

被引：26

作者：

Chen, Ying ^{[1
]}

Moiseyev, Gennadiy ^{[1
]}

Takahashi, Yusuke ^{[1
]}

Ma, Jian-xing ^{[1
]}

机构：

[1] Univ Oklahoma, Hlth Sci Ctr, Dept Med Endocrinol, Dept Cell Biol, Oklahoma City, OK 73104 USA

来源：

FEBS LETTERS | 2006年 / 580卷 / 17期

关键词：

LRAT; retinoid; retinal degeneration; RPE; RPE65; visual cycle;

D O I：

10.1016/j.febslet.2006.06.078

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：4200 / 4204

页数：5

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