Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport
Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport
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DOI：
10.1038/10084
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发表时间：
1999-06-01
影响因子：
21.3
通讯作者：
Gruenberg, J
中科院分区：
文献类型：
--
作者：
Kobayashi, T;Beuchat, MH;Gruenberg, J
低密度脂蛋白内吞后释放的游离胆固醇的命运仍然不明。在此，我们报告了晚期内小体在细胞内胆固醇运输中起着关键作用。我们发现，在遗传性疾病Niemann-Pick C型(NPC)中，以及在模拟NPC的药物治疗细胞中，胆固醇在晚期内吞体内积聚，溶酶体酶受体的分选受到损害。我们的结果表明，包含在多囊晚期内体中的富含溶酶双磷脂酸的膜的特征网络调节胆固醇的运输，可能是通过作为收集和分配装置来发挥作用的。研究结果还表明，抗磷脂综合征和鼻咽癌患者也存在类似的内体缺陷。
The fate of free cholesterol released after endocytosis of low-density lipoproteins remains obscure. Here we report that late endosomes have a pivotal role in intracellular cholesterol transport. We find that in the genetic disease Niemann-Pick type C (NPC), and in drug-treated cells that mimic NPC, cholesterol accumulates in late endosomes and sorting of the lysosomal enzyme receptor is impaired. Our results show that the characteristic network of lysobisphosphatidic acid-rich membranes contained within multivesicular late endosomes regulates cholesterol transport, presumably by acting as a collection and distribution device. The results also suggest that similar endosomal defects accompany the anti-phospholipid syndrome and NPC.