Transmembrane Molecular Pump Activity of Niemann-Pick C1 Protein-Reference-Cited by-同舟云学术

Transmembrane Molecular Pump Activity of Niemann-Pick C1 Protein

Published:2000-12-22 Issue:5500 Volume:290 Page:2295-2298
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Davies Joanna P.¹,Chen Fannie W.¹,Ioannou Yiannis A.¹

Affiliation:

1. Department of Human Genetics, Box 1498, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference28 articles.

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