ABC proteins: key molecules for lipid homeostasis
ABC proteins: key molecules for lipid homeostasis
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DOI：
10.1007/s00795-004-0278-8
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发表时间：
2005-03-01
影响因子：
1.8
通讯作者：
Ueda, Kazumitsu
中科院分区：
文献类型：
--
作者：
Takahashi, Kei;Kimura, Yasuhisa;Ueda, Kazumitsu
人类染色体上存在49个ABC蛋白基因。真核细胞ABC蛋白最初被认为是参与癌细胞多药耐药的药物外排泵。然而，现在认识到它们的主要生理作用之一是细胞脂质转运和稳态，并且它们的功能障碍通常与人类疾病有关。ABCA 1和ABCA 7介导高密度脂蛋白-胆固醇复合物的载脂蛋白依赖性形成。ABCA 3是肺表面活性物质分泌所必需的。ABCG 5和ABCG 8参与将植物甾醇和胆固醇分泌到胆汁中。然而，这些ABC蛋白的主要底物和作用机制尚未精确定义。在这篇综述文章中，我们首先描述了真核生物ABC蛋白的一般结构和功能。ABCA 1功能的当前模型，然后解释的基础上的拓扑模型，亚细胞定位，apoA-I的HDL形成的依赖性，丹吉尔病突变体的功能缺陷的研究。和纯化的ABCA 1的ATP水解。ABCA 1被认为是脂质转运蛋白和apoA-I受体。ABCA 3可能参与在板层体中积累磷脂和胆固醇以及产生多泡结构。
Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is Cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein-cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants. and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures.