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K. Boesze-Battaglia, T. Diemer, C. Lillo, M. Damek-Poprawa, D. Williams; A Role for Melanoregulin (MREG) in RPE Mediated Phagocytosis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2514.
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© ARVO (1962-2015); The Authors (2016-present)
Melanoregulin (MREG), a recently cloned product of the dilute suppressor (dsu) locus, is a unique 28 kDa protein, present in human, mouse and rat RPE cells. MREG suppresses the coat-color phenotype of three pigment mutations encoding for a melanosome transport system and is involved in organelle biogenesis. In this study we we analyzed the effect of loss of MREG in RPE- dependent processes; specifically phagocytosis.
Ultrastructure of MREG null RPE was analyzed by TEM. MREG localization was assessed using confocal microscopy of retinal frozen sections as well as Immuno-EM. Phagocytosis was followed using an ex- vivo cell culture assay. MREG protein binding partners were analyzed by co-immunoprecipitation.
MREG null mice exhibited an increase in the number of phagosomes both at lights on and three hours later. When the kinetics of OS disk membrane phagocytosis by the RPE were assayed, using an ex vivo cell culture assay, loss of MREG was shown to result in a decrease in the rate of OS phagosome digestion, with little change in the binding or ingestion phases of the process. To begin to understand the role of MREG in the phagocytic process we generated a series of anti-MREG monoclonal antibodies. In co-immunoprecipitaion studies, MREG was found to interact with MerTK and in OS extracts with the C-terminus of RDS. In addition, MREG co-localized with RPE apical membrane rafts. Ultrastructural analysis localized MREG to small vesicles in the RPE cytoplasm, consistent with a role for this protein in regulating membrane interactions following the ingestion phase of phagocytosis.
Collectively, these studies suggest that MREG may play a regulatory role in the catabolic phase of OS disk membrane renewal.
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