Journal
JOURNAL OF CELL SCIENCE
Volume 124, Issue 4, Pages 523-531Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.078790
Keywords
beta A3/A1-crystallin; Cathepsin D; Retinal pigmented epithelium ( RPE); Photoreceptor outer segment discs; Lysosome; Phagocytosis; Autophagy
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Funding
- National Institutes of Health [EY018636, EY019037, EY019037-S, EY09357, EY016151-5, EY14005, EY01765]
- National Eye Institute
- Helena Rubinstein Foundation
- Research to Prevent Blindness
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Phagocytosis of the shed outer segment discs of photoreceptors is a major function of the retinal pigmented epithelium (RPE). We demonstrate for the first time that beta A3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the beta A3/A1-crystallin gene is mutated, we show that this protein is required by RPE cells for proper degradation of outer segment discs that have been internalized in phagosomes. We also demonstrate that in wild-type RPE, beta A3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, beta A3/A1-crystallin fails to translocate to the lysosomes, perhaps because misfolding of the mutant protein masks sorting signals required for proper trafficking. The digestion of phagocytized outer segments requires a high level of lysosomal enzyme activity, and cathepsin D, the major enzyme responsible for proteolysis of the outer segments, is decreased in mutant RPE cells. Interestingly, our results also indicate a defect in the autophagy process in the Nuc1 RPE, which is probably also linked to impaired lysosomal function, because phagocytosis and autophagy might share common mechanisms in degradation of their targets. beta A3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.
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