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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake
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Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake

机译：Flotillins在Niemann-Pick C1样1介导的胆固醇摄取中起重要作用

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摘要

Dietary absorption is a major way for mammals to obtain cholesterol, which is mediated by Niemann-Pick C1-like 1 (NPC1L1) via vesicular endocytosis. One fundamental question in this process is how free cholesterol is efficiently taken up through the interna-lization of NPC1L1. Using exogenously expressed NPC1L1-EGFP, we show that the lipid raft proteins flotillins associate with NPC1L1 and their localization is regulated by NPC1L1 during intracellular trafficking. Furthermore, flotillins are essential for NPC1L1-mediated cellular cholesterol uptake, biliary cholesterol reabsorption, and the regulation of lipid levels in mice. Together with NPC1L1, they form cholesterol-enriched membrane microdomains, which function as carriers for bulk of cholesterol. The hypocholesterole-mic drug ezetimibe disrupts the association between NPC1L1 and flotillins, which blocks the formation of the cholesterol-enriched microdomains. Our findings reveal a functional role of flotillins in NPC1L1-mediated cholesterol uptake and elucidate the formation of NPC1L1-flotillins-postive cholesterol-enriched membrane microdomains as a mechanism for efficient cholesterol absorption.
机译：饮食吸收是哺乳动物获得胆固醇的主要途径，胆固醇是由Niemann-Pick C1样1（NPC1L1）通过囊泡内吞作用介导的。这个过程中的一个基本问题是如何通过NPC1L1的国际化有效地吸收游离胆固醇。使用外源表达的NPC1L1-EGFP，我们显示脂质筏蛋白flotillins与NPC1L1相关联，并且它们的定位在细胞内运输过程中受NPC1L1调控。此外，弗洛蒂林对NPC1L1介导的细胞胆固醇摄取，胆汁胆固醇重吸收和小鼠脂质水平的调节至关重要。它们与NPC1L1一起形成富含胆固醇的膜微区，其充当大量胆固醇的载体。降胆固醇的药物依泽替米贝破坏了NPC1L1与弗洛蒂林之间的缔合，从而阻止了富含胆固醇的微区的形成。我们的发现揭示了絮状蛋白在NPC1L1介导的胆固醇摄取中的功能性作用，并阐明了NPC1L1-絮凝素阳性的富含胆固醇的膜微区的形成，作为有效吸收胆固醇的机制。

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    Liang Ge; Wei Qi; Li-Juan Wang; Hong-Hua Miao; Yu-Xiu Qu; Bo-Liang Li; Bao-Liang Song;

  • 作者单位

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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