RPE65 is the isomerohydrolase in the retinoid visual cycle
RPE65 is the isomerohydrolase in the retinoid visual cycle
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DOI：
10.1073/pnas.0503460102
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发表时间：
2005-08-30
影响因子：
11.1
通讯作者：
Ma, JX
中科院分区：
文献类型：
--
作者：
Moiseyev, G;Chen, Y;Ma, JX
RPE 65是视网膜色素上皮中丰富的蛋白质。RPE 65的突变与遗传性视网膜营养不良有关。尽管已知RPE 65对于视觉周期中11-顺式视黄醇的再生是关键的，但RPE 65的功能是难以捉摸的。在这里，我们表明，重组RPE 65，当在QBI-293 A和COS-1细胞中表达时，具有强大的酶活性的先前未鉴定的异构水解酶，酶转化全反式视黄酯11-顺式视黄醇在视觉循环。反应的初始速率为2.9pmol/min/mg在293 A细胞中表达的RPE 65。RPE 65的异构水解酶活性需要卵磷脂视黄醇酰基转移酶在同一细胞中共表达以提供其底物。这种酶活性线性依赖于IRPE 65的表达水平。这项研究表明，RPE 65是长期寻找的异构水解酶，填补了我们对视觉周期理解的一个主要空白。RPE 65功能的鉴定将有助于理解与RPE 65突变相关的视网膜营养不良的发病机制。
RPE65 is an abundant protein in the retinal pigment epithelium. Mutations in RPE65 are associated with inherited retinal dystrophies. Although it is known that RPE65 is critical for regeneration of 1 1-cis retinol in the visual cycle, the function of RPE65 is elusive. Here we show that recombinant RPE65, when expressed in QBI-293A and COS-1 cells, has robust enzymatic activity of the previous unidentified isomerohydrolase, an enzyme converting all-trans retinyl ester to 11-cis retinol in the visual cycle. The initial rate for the reaction is 2.9 pmol/min per mg of RPE65 expressed in 293A cells. The isomerohydrolase activity of RPE65 requires coexpression of lecithin retinol acyltransferase in the same cell to provide its substrate. This enzymatic activity is linearly dependent on the expression levels of IRPE65. This study demonstrates that RPE65 is the long-sought isomerohydrolase and fills a major gap in our understanding of the visual cycle. Identification of the function of RPE65 will contribute to the understanding of the pathogenesis for retinal dystrophies associated with RPE65 mutations.