黑素调节蛋白（MREG）调节色素上皮细胞中的溶酶体功能。
Melanoregulin (MREG) modulates lysosome function in pigment epithelial cells.
作者信息
Damek-Poprawa Monika, Diemer Tanja, Lopes Vanda S, Lillo Concepción, Harper Dawn C, Marks Michael S, Wu Yalin, Sparrow Janet R, Rachel Rivka A, Williams David S, Boesze-Battaglia Kathleen
机构信息
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
出版信息
J Biol Chem. 2009 Apr 17;284(16):10877-89. doi: 10.1074/jbc.M808857200. Epub 2009 Feb 23.
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.
黑素调节蛋白（MREG）是Mreg(dsu)基因的产物，是一种高度带电荷的小蛋白，由于其对稀释、灰白色和铅灰色突变小鼠色素沉着的影响，被认为在细胞器生物发生中起作用。在此，我们提供证据表明MREG在溶酶体依赖性吞噬体降解中是必需的。在Mreg(-/-)小鼠中，我们发现MREG功能丧失导致吞噬体积累，这是由于被吞噬物质降解延迟所致。随着时间的推移，Mreg(-/-)小鼠视网膜色素上皮细胞积累了脂褐素成分A2E。由于加工缺陷，MREG缺陷的人和小鼠视网膜色素上皮细胞中溶酶体水解酶组织蛋白酶D的活性降低。此外，MREG定位于小的细胞内囊泡，并与内体磷酸肌醇磷脂酰肌醇3,5-二磷酸相关联。这些研究共同表明，MREG是溶酶体成熟所必需的，并支持MREG在细胞内运输中的作用。
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