Transmembrane molecular pump activity of Niemann-Pick C1 protein

被引：235

作者：

Davies, JP ^{[1
]}

Chen, FW ^{[1
]}

Ioannou, YA ^{[1
]}

机构：

[1] CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA

来源：

SCIENCE | 2000年 / 290卷 / 5500期

关键词：

D O I：

10.1126/science.290.5500.2295

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Niemann-Pick C1 (NPC1) disease is characterized by cholesterol accumulation in Lysosomes and aberrant feedback regulation of cellular cholesterol homeostasis, We provide evidence that the NPC1 protein has homology with the resistance-nodulation-division (RND) family of prokaryotic permeases and may normally function as a transmembrane efflux pump, Studies of acriflavine Loading in normal and NPC1 fibroblasts indicated that NPC1 uses a proton motive force to remove accumulated acriflavine from the endosomal/lysosomal system. Expression of NPC1 in Escherichia coli (i) facilitated the transport of acriflavine across the plasma membrane, causing cytosolic accumulation, and (ii) resulted in transport of oleic acid but not cholesterol or cholesterol-oleate across the plasma membrane. These studies establish NPC1 as a eukaryotic member of the RND permease family.

引用

页码：2295 / +

页数：5

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