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首页> 外文期刊>Journal of Molecular Biology >ABCB6 Resides in Melanosomes and Regulates Early Steps of Melanogenesis Required for PMEL Amyloid Matrix Formation
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ABCB6 Resides in Melanosomes and Regulates Early Steps of Melanogenesis Required for PMEL Amyloid Matrix Formation

机译：ABCB6驻留在黑色素体中，并调节PMEL淀粉样蛋白基质形成所需的糖胺的早期步骤

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摘要

Genetically inheritable pigmentation defects provide a unique opportunity to reveal the function of proteins contributing to melanogenesis. Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary genodermatosis associated with mutations in the ABCB6 gene. Here we use optical and electron microscopy imaging combined with biochemical tools to investigate the localization and function of ABCB6 in pigment cells. We show that ABCB6 localizes to the membrane of early melanosomes and lysosomes of the human melanocytic cell line MNT-1. Depletion of ABCB6 by siRNA impaired PMEL amyloidogenesis in early melanosomes and induced aberrant accumulation of multilamellar aggregates in pigmented melanosomes. PMEL fibril formation and normal maturation of pigmented melanosomes could be restored by the overexpression of wild-type ABCB6 but not by variants containing an inactivating catalytic mutation (K629M) or the G579E DUH mutation. In line with the impairment of PMEL matrix formation in the absence of ABCB6, morphological analysis of the retinal pigment epithelium of ABCB6 knockout mice revealed a significant decrease of melanosome numbers. Our study extends the localization of ABCB6 to melanosomes, suggesting a potential link between the function of ABCB6 and the etiology of DUH to amyloid formation in pigment cells. (C) 2018 Elsevier Ltd. All rights reserved.
机译：基因上可遗传的色素沉着缺陷提供了揭示蛋白质促进糖酵母的功能的独特机会。 Dyschromatosis Universalis肠道（DUH）是一种罕见的色素发生变种，与ABCB6基因中的突变相关。在这里，我们使用光学和电子显微镜成像结合生化工具来研究ABCB6在颜料细胞中的定位和功能。我们表明ABCB6定位于人黑素细胞系MNT-1的早期黑素体和溶酶体的膜。 SiRNA在早期黑色素中的PMEL淀粉样蛋白生成的ABCB6耗尽，并在色素沉浸式黑色素中诱导多样性聚集体的异常积累。可以通过野生型ABCB6的过表达来恢复PMEL原纤维形成和正常成熟的色素染色的黑色素，但不是含有灭活催化突变（K629M）或G579E DUH突变的变体。符合PMEL基质形成在没有ABCB6的情况下，ABCB6敲除小鼠的视网膜色素上皮的形态分析显示了黑素体数的显着降低。我们的研究将ABCB6的定位延伸到黑素体，表明ABCB6功能与颜料细胞中DUH至淀粉样蛋白形成的病因之间的潜在联系。 （c）2018年elestvier有限公司保留所有权利。

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