Weng J, Mata N L, Azarian S M, Tzekov R T, Birch D G, Travis G H
Center for Basic Neuroscience and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Cell. 1999 Jul 9;98(1):13-23. doi: 10.1016/S0092-8674(00)80602-9.
Rim protein (RmP) is an ABC transporter of unknown function in rod outer segment discs. The human gene for RmP (ABCR) is affected in several recessive retinal degenerations. Here, we characterize the ocular phenotype in abcr knockout mice. Mice lacking RmP show delayed dark adaptation, increased all-trans-retinaldehyde (all-trans-RAL) following light exposure, elevated phosphatidylethanolamine (PE) in outer segments, accumulation of the protonated Schiff base complex of all-trans-RAL and PE (N-retinylidene-PE), and striking deposition of a major lipofuscin fluorophore (A2-E) in retinal pigment epithelium (RPE). These data suggest that RmP functions as an outwardly directed flippase for N-retinylidene-PE. Delayed dark adaptation is likely due to accumulation in discs of the noncovalent complex between opsin and all-trans-RAL. Finally, ABCR-mediated retinal degeneration may result from "poisoning" of the RPE due to A2-E accumulation, with secondary photoreceptor degeneration due to loss of the RPE support role.
边缘蛋白（RmP）是视杆细胞外段盘膜中一种功能未知的ABC转运蛋白。人类RmP基因（ABCR）在几种隐性视网膜变性中受到影响。在此，我们对abcr基因敲除小鼠的眼部表型进行了特征描述。缺乏RmP的小鼠表现出暗适应延迟、光照后全反式视黄醛（all-trans-RAL）增加、外段中磷脂酰乙醇胺（PE）升高、全反式视黄醛与PE的质子化席夫碱复合物（N-视黄叉-PE）积累，以及视网膜色素上皮（RPE）中主要脂褐素荧光团（A2-E）的显著沉积。这些数据表明RmP作为N-视黄叉-PE的外向翻转酶发挥作用。暗适应延迟可能是由于视蛋白与全反式视黄醛之间的非共价复合物在盘膜中积累所致。最后，ABCR介导的视网膜变性可能是由于A2-E积累导致RPE“中毒”，继而因RPE支持作用丧失而导致光感受器继发性变性。
