Melanoregulin (MREG) Modulates Lysosome Function in Pigment Epithelial Cells

被引：38

作者：

Damek-Poprawa, Monika ^{[1
]}

Diemer, Tanja ^{[2
,3
,4
]}

Lopes, Vanda S. ^{[2
]}

Lillo, Concepcion ^{[3
,4
]}

Harper, Dawn C.

Marks, Michael S.

Wu, Yalin ^{[5
]}

Sparrow, Janet R. ^{[5
,6
]}

Rachel, Rivka A. ^{[7
]}

Williams, David S. ^{[2
,3
,4
]}

Boesze-Battaglia, Kathleen ^{[1
]}

机构：

[1] Univ Penn, Dept Biochem, Sch Dent Med, Philadelphia, PA 19104 USA

[2] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA

[3] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[5] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[6] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[7] NEI, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 16期

基金：

美国国家卫生研究院;

关键词：

MURINE DILUTE SUPPRESSOR; AGE-RELATED-CHANGES; COAT-COLOR PHENOTYPE; CATHEPSIN-D; OUTER SEGMENTS; DEGRADATIVE FUNCTIONS; RETINOID COMPONENT; RPE LIPOFUSCIN; GENE DSU; A2E;

D O I：

10.1074/jbc.M808857200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：10877 / 10889

页数：13

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