Melanoregulin (MREG) Modulates Lysosome Function in Pigment Epithelial Cells
Melanoregulin (MREG) Modulates Lysosome Function in Pigment Epithelial Cells
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DOI：
10.1074/jbc.m808857200
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发表时间：
2009-04-17
影响因子：
4.8
通讯作者：
Boesze-Battaglia, Kathleen
中科院分区：
文献类型：
--
作者：
Damek-Poprawa, Monika;Diemer, Tanja;Boesze-Battaglia, Kathleen
Melanoregulin（MREG），Mreg（dsu）基因的产物，是一种小的高度带电的蛋白质，由于其对稀释、灰白和铅质突变小鼠的色素沉着的影响，推测其在细胞器生物发生中发挥作用。在这里，我们提供的证据表明，MREG是必需的溶酶体依赖性吞噬体降解。在Mreg（-/-）小鼠中，我们发现MREG功能的丧失导致吞噬体蓄积，这是由于吞噬物质的延迟降解。随着时间的推移，Mreg（-/-）小鼠视网膜色素上皮细胞积累脂褐质组分A2 E。由于加工缺陷，MREG缺陷的人和小鼠视网膜色素上皮细胞表现出溶酶体水解酶（组织蛋白酶D）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3，5-二磷酸缔合。总的来说，这些研究表明，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。
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.