title: Melanoregulin (MREG) modulates lysosome function in pigment epithelial cells.
abstract: Melanoregulin (MREG), the product of the Mreg(dsu) gene, is a small highly charged protein, hypothesized to play a role in organelle biogenesis due to its effect on pigmentation in dilute, ashen, and leaden mutant mice. Here we provide evidence that MREG is required in lysosome-dependent phagosome degradation. In the Mreg(-/-) mouse, we show that loss of MREG function results in phagosome accumulation due to delayed degradation of engulfed material. Over time, the Mreg(-/-) mouse retinal pigment epithelial cells accumulate the lipofuscin component, A2E. MREG-deficient human and mouse retinal pigment epithelial cells exhibit diminished activity of the lysosomal hydrolase, cathepsin D, due to defective processing. Moreover, MREG localizes to small intracellular vesicles and associates with the endosomal phosphoinositide, phosphatidylinositol 3,5-biphosphate. Collectively, these studies suggest that MREG is required for lysosome maturation and support a role for MREG in intracellular trafficking.
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Damek-Poprawa
authors.forename: Tanja
authors.initials: T
authors.lastname: Diemer
authors.forename: Vanda S
authors.initials: VS
authors.lastname: Lopes
authors.forename: Concepción
authors.initials: C
authors.lastname: Lillo
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Harper
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marks
authors.forename: Yalin
authors.initials: Y
authors.lastname: Wu
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
authors.forename: Rivka A
authors.initials: RA
authors.lastname: Rachel
authors.forename: David S
authors.initials: DS
authors.lastname: Williams
authors.forename: Kathleen
authors.initials: K
authors.lastname: Boesze-Battaglia
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008062:Lipofuscin / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology; D010714:Phosphatidylethanolamines / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology*; D011726:Pyridinium Compounds / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012172:Retinaldehyde / Q000031:analogs & derivatives / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008062:Lipofuscin; D010714:Phosphatidylethanolamines; D018129:Phosphatidylinositol Phosphates; D011726:Pyridinium Compounds; D034741:RNA, Small Interfering; D012176:Retinoids; C518334:melanoregulin protein, mouse; C106336:phosphatidylinositol 3,5-diphosphate; C525877:retinal dimer phosphatidylethanolamine; D002402:Cathepsin D; D012172:Retinaldehyde