Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, LA, USA.
Department of Ophthalmology, Louisiana State University School of Medicine, New Orleans, LA, USA.
FEBS Lett. 2020 Feb;594(3):540-552. doi: 10.1002/1873-3468.13633. Epub 2019 Oct 20.
The retinal pigment epithelium-specific 65 kDa (RPE65) isomerase plays a pivotal role in photoreceptor survival and function. RPE65-catalyzed synthesis of 11-cis-retinol from all-trans-retinyl esters in the visual cycle is negatively regulated, through a heretofore unknown mechanism, by the fatty acid transport protein FATP4, mutations in which are associated with ichthyosis prematurity syndrome (IPS). Here, we analyzed the interaction between deletion mutants of FATP4 and RPE65 and the impacts of IPS-associated FATP4 mutations on RPE65 expression, 11-cis-retinol synthesis, and all-trans-retinyl ester synthesis. Our results suggest that the interaction between FATP4 and RPE65 contributes to the inhibition of RPE65 function and that IPS-associated nonsense and missense mutations in FATP4 have different effects on the visual cycle.
视网膜色素上皮细胞特异性 65kDa（RPE65）异构酶在感光细胞存活和功能中起着关键作用。通过迄今为止未知的机制，脂肪酸转运蛋白 FATP4 负调控视循环中全反式视黄醇酯向 11-顺式视黄醇的合成，该蛋白的突变与鱼鳞病早发性综合征（IPS）有关。在这里，我们分析了 FATP4 和 RPE65 的缺失突变体之间的相互作用，以及 IPS 相关的 FATP4 突变对 RPE65 表达、11-顺式视黄醇合成和全反式视黄醇酯合成的影响。我们的结果表明，FATP4 和 RPE65 之间的相互作用有助于抑制 RPE65 的功能，并且 IPS 相关的 FATP4 无义和错义突变对视觉循环有不同的影响。
