RT Journal Article
SR Electronic
T1 Mutation in the βA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 523
OP 531
DO 10.1242/jcs.078790
VO 124
IS 4
A1 Zigler, J. Samuel
A1 Zhang, Cheng
A1 Grebe, Rhonda
A1 Sehrawat, Gitanjali
A1 Hackler, Laszlo
A1 Adhya, Souvonik
A1 Hose, Stacey
A1 McLeod, D. Scott
A1 Bhutto, Imran
A1 Barbour, Walid
A1 Parthasarathy, Geetha
A1 Zack, Donald J.
A1 Sergeev, Yuri
A1 Lutty, Gerard A.
A1 Handa, James T.
A1 Sinha, Debasish
YR 2011
UL http://jcs.biologists.org/content/124/4/523.abstract
AB 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 βA3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the βA3/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, βA3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, βA3/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. βA3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.