Kobayashi T, Beuchat M H, Lindsay M, Frias S, Palmiter R D, Sakuraba H, Parton R G, Gruenberg J
Department of Biochemistry, University of Geneva, Switzerland.
Nat Cell Biol. 1999 Jun;1(2):113-8. doi: 10.1038/10084.
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.
低密度脂蛋白内吞作用后释放的游离胆固醇的去向仍不清楚。在此我们报告，晚期内体在细胞内胆固醇转运中起关键作用。我们发现，在遗传性疾病尼曼-皮克C型（NPC）以及模拟NPC的药物处理细胞中，胆固醇在晚期内体中积累，溶酶体酶受体的分选受损。我们的结果表明，多泡晚期内体中富含溶血双磷脂酸的膜的特征性网络调节胆固醇转运，大概是通过充当收集和分配装置来实现的。结果还表明，抗磷脂综合征和NPC伴有类似的内体缺陷。
