Department of Biological Sciences and Biotechnology, State-Key Lab of Biomembranes and Membrane Biotechnology, Tsinghua University, Haidian District, 100084 Beijing, China.
Mol Biol Rep. 2011 Jun;38(5):2869-77. doi: 10.1007/s11033-010-9948-x. Epub 2010 Jan 28.
Study of retina specific genes would offer insights into retinal diseases and treatment. Based on the information from the gene expression profiles of mouse retinas, we here identified a mitochondria-localized glutamic acid-rich protein (MGARP/OSAP) as one of the highly expressed proteins in retina. Sequence analysis revealed that mouse and rat MGARPs have an extra insertion of four consecutive amino acid repeats at the C-terminus, while other homologues do not. MGARP was demonstrated to be localized to the mitochondria and overexpression of MGARP missing N-terminal region causes severe mitochondrial aggregation, implying an important role of MGARP in maintaining mitochondrial morphology. MGARP is highly expressed in mitochondria-rich layers, including inner segment of the photoreceptor, outer plexiform layer and ganglion cell layers of mouse retina. Far-UV CD spectrum analysis suggested that MGARP exhibits a large area of intrinsic disorder and the unusual position of its Tyr fluorescence suggested that Tyr residues in MGARP might form excimer and exist in an ionized state. These findings implied that MGARP be a good candidate for assembling certain ion channels on mitochondria membrane and have great potential to be involved in retinal energetic metabolism through mitochondria related pathway.
对视网膜特异性基因的研究将为视网膜疾病的治疗提供新的思路。基于对小鼠视网膜基因表达谱的信息分析，我们在此鉴定出一个定位于线粒体的谷氨酸丰富蛋白（MGARP/OSAP）作为在视网膜中高度表达的蛋白之一。序列分析表明，鼠和大鼠的 MGARPs 在 C 端有四个连续氨基酸重复的额外插入，而其他同源物则没有。MGARP 被证明定位于线粒体，并且 MGARP 缺失 N 端区域的过表达会导致严重的线粒体聚集，这表明 MGARP 在维持线粒体形态方面起着重要作用。MGARP 在富含线粒体的层中高度表达，包括光感受器的内节、外丛状层和鼠视网膜的节细胞层。远紫外 CD 光谱分析表明，MGARP 表现出较大的固有无序区，其 Tyr 荧光的异常位置表明，MGARP 中的 Tyr 残基可能形成二聚体并处于离子化状态。这些发现表明，MGARP 可能是组装线粒体膜上某些离子通道的良好候选物，并有可能通过与线粒体相关的途径参与视网膜能量代谢。
