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首页> 外文期刊>Current opinion in lipidology >The structure and function of Niemann-Pick C1-like 1 protein.
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The structure and function of Niemann-Pick C1-like 1 protein.

机译：Niemann-Pick C1样1蛋白的结构和功能。

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PURPOSE OF REVIEW: Intestinal absorption and biliary excretion of cholesterol represent two major pathways by which the body regulates cholesterol homeostasis. Niemann-Pick C1-like 1 (NPC1L1) is a polytopic transmembrane protein containing a sterol-sensing domain of unknown function. In 2004, NPC1L1 was identified to be essential for intestinal cholesterol absorption, a process that is sensitive to a cholesterol absorption inhibitor ezetimibe. This review summarizes recent studies on NPC1L1 function and proposes a model for NPC1L1-dependent cholesterol uptake. RECENT FINDINGS: Cell culture experiments have shown that NPC1L1 mediates cellular uptake of various sterols but seems to have lower affinity to plant sterols than cholesterol. Transgenic animal studies have demonstrated that hepatic NPC1L1 has the potential to regulate biliary cholesterol excretion. Cholesterol and many transcriptional factors appear to regulate NPC1L1 gene expression. NPC1L1 protein is enriched in the apical membrane of polarized cells and its intracellular itineraries are clearly regulated by cholesterol availability. Evidence suggests cholesterol-regulated clathrin-mediated endocytosis is likely the cellular basis for NPC1L1-dependent cholesterol uptake, which may reconcile disagreement regarding NPC1L1 subcellular localization. SUMMARY: NPC1L1 may have evolved at two sites (apical membrane of enterocytes and canalicular membrane of hepatocytes) to mediate cholesterol uptake through a clathrin-mediated endocytic process, protecting the body against fecal and biliary loss of cholesterol.
机译：审查目的：胆固醇的肠道吸收和胆汁排泄是人体调节胆固醇稳态的两个主要途径。 Niemann-Pick C1样1（NPC1L1）是一种多位跨膜蛋白，包含功能未知的固醇感应结构域。 2004年，NPC1L1被确定为肠道胆固醇吸收所必需的，该过程对胆固醇吸收抑制剂依泽替米贝敏感。这篇综述总结了有关NPC1L1功能的最新研究，并提出了NPC1L1依赖性胆固醇摄取的模型。最近的发现：细胞培养实验表明NPC1L1介导细胞吸收各种固醇，但似乎对植物固醇的亲和力比胆固醇低。转基因动物研究表明，肝NPC1L1具有调节胆汁胆固醇排泄的潜力。胆固醇和许多转录因子似乎调节NPC1L1基因表达。 NPC1L1蛋白富集在极化细胞的顶膜中，其细胞内行程明显受胆固醇的利用。有证据表明，胆固醇调节的网格蛋白介导的内吞作用可能是NPC1L1依赖性胆固醇摄取的细胞基础，这可以调和关于NPC1L1亚细胞定位的分歧。简介：NPC1L1可能已经在两个部位（肠上皮细胞的顶膜和肝细胞的小管膜）进化，以通过网格蛋白介导的内吞过程介导胆固醇的摄取，从而保护人体免受粪便和胆汁中胆固醇的损失。

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