Transport of lipids from Golgi to plasma membrane is defective in Tangier disease patients and Abc1-deficient mice
Transport of lipids from Golgi to plasma membrane is defective in Tangier disease patients and Abc1-deficient mice
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DOI：
10.1038/72869
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发表时间：
2000-02-01
期刊：
影响因子：
30.8
通讯作者：
Schmitz, G
中科院分区：
文献类型：
--
作者：
Orsó, E;Broccardo, C;Schmitz, G
丹吉尔病（TD）是一种常染色体隐性遗传病，其特征是血浆高密度脂蛋白（HDL）几乎完全缺失，网状内皮系统（RES）中胆固醇酯沉积(4)和细胞脂质转运异常（5-12）。我们在这里证明，Abc1靶向失活的小鼠表现出与TD一致的形态异常和脂蛋白代谢紊乱。ABC1在质膜和高尔基复合体上表达，介导载脂蛋白al相关的胆固醇和磷脂从细胞输出，并受胆固醇通量调节。缺乏功能性ABC1的细胞的空泡加工和反高尔基体分泌途径的结构和功能异常表明，涉及高尔基体和质膜之间水泡出芽的脂质输出过程受到严重干扰。
Mutations in the gene encoding ATP-binding cassette transporter 1 (ABC1) have been reported in Tangier disease(1-3) (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system(4) (RES) and aberrant cellular lipid trafficking(5-12). We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-Al associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed.