Transmembrane molecular pump activity of Niemann-Pick C1 protein

J. P. Davies, F. W. Chen, Y. A. Ioannou

Research output: Contribution to journalArticlepeer-review

266 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2295-2298
Number of pages4
JournalScience
Volume290
Issue number5500
DOIs
StatePublished - 22 Dec 2000

Fingerprint

Dive into the research topics of 'Transmembrane molecular pump activity of Niemann-Pick C1 protein'. Together they form a unique fingerprint.

Cite this