Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells
Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells
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DOI：
10.1074/jbc.m107876200
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发表时间：
2002-05-10
影响因子：
4.8
通讯作者：
Vollrath, D
中科院分区：
文献类型：
--
作者：
Feng, W;Yasumura, D;Vollrath, D
RCS大鼠是一种被广泛研究的隐性遗传性视网膜变性模型。这种遗传缺陷被称为rdy（视网膜营养不良），导致视网膜色素上皮（RPE）吞噬脱落的光感受器外段膜的功能失败。我们以前使用位置克隆和体内遗传互补来证明Mertk是rdy的基因。我们现在使用了大鼠原代RPE细胞培养系统。证明RPE是Mertk的作用部位，并获得Mertk在RPE吞噬中起关键作用的功能证据。我们发现Mertk蛋白在RCS中不存在，而在野生型组织和培养的RPE细胞中不存在。通过重组腺病毒将Mertk传递到培养的RCS RPE细胞，使细胞恢复完全的吞噬能力。感染的RCS RPE细胞摄取外源性外段的程度与野生型RPE细胞相同，但外段结合不受影响。Mertk蛋白在原代RPE细胞吞噬过程中逐渐与外段物质共定位，激活了RPE- j细胞吞噬早期积累的Mertk。我们得出结论，Mertk可能直接在RPE吞噬过程中起作用，作为触发外段摄取的信号分子。
The RCS rat is a widely studied model of recessively inherited retinal degeneration. The genetic defect, known as rdy (retinal dystrophy), results in failure of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer segment membranes. We previously used positional cloning and in vivo genetic complementation to demonstrate that Mertk is the gene for rdy. We have now used a rat primary RPE cell culture system. to demonstrate that the RPE is the site of action of Mertk and to obtain functional evidence for a key role of Mertk in RPE phagocytosis. We found that Mertk protein is absent from RCS, but not wild-type, tissues and cultured RPE cells. Delivery of rat Mertk to cultured RCS RPE cells by means of a recombinant adenovirus restored the cells to complete phagocytic competency. Infected RCS RPE cells ingested exogenous outer segments to the same extent as wild-type RPE cells, but outer segment binding was unaffected. Mertk protein progressively co-localized with outer segment material during phagocytosis by primary RPE cells, and activated Mertk accumulated during the early stages of phagocytosis by RPE-J cells. We conclude that Mertk likely functions directly in the RPE phagocytic process as a signaling molecule triggering outer segment ingestion.