MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
Mertk Triggers Uptake of Photoreceptor Outer Segments during Phagocytosis by Cultured Retinal Pigment Epithelial Cells*

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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 andin vivo genetic complementation to demonstrate thatMertk 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.

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Published, JBC Papers in Press, February 22, 2002, DOI 10.1074/jbc.M107876200

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This work was supported by a postdoctoral fellowship from the Fight for Sight research division of Prevent Blindness America (to W. F.), by grants from the Ruth and Milton Steinbach Fund and the Karl Kirchgessner Foundation (to D. V.), by National Institutes of Health Grants EY01919, EY02162, and EY06842, the Foundation Fighting Blindness, and the Macula Vision Research Foundation (to M. M. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Research to Prevent Blindness Senior Scientist Investigator.