A Role for Oxysterol-binding Protein-related Protein 5 in Endosomal Cholesterol Trafficking

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2011 Jan 12

PMID 21220512

Citations 137

Authors

Ximing Du

Jaspal Kumar

Charles Ferguson

Timothy A Schulz

Yan Shan Ong

Wanjin Hong

William A Prinz

Robert G Parton

Andrew J Brown

Hongyuan Yang

Affiliations

Soon will be listed here.

Abstract

Oxysterol-binding protein (OSBP) and its related proteins (ORPs) constitute a large and evolutionarily conserved family of lipid-binding proteins that target organelle membranes to mediate sterol signaling and/or transport. Here we characterize ORP5, a tail-anchored ORP protein that localizes to the endoplasmic reticulum. Knocking down ORP5 causes cholesterol accumulation in late endosomes and lysosomes, which is reminiscent of the cholesterol trafficking defect in Niemann Pick C (NPC) fibroblasts. Cholesterol appears to accumulate in the limiting membranes of endosomal compartments in ORP5-depleted cells, whereas depletion of NPC1 or both ORP5 and NPC1 results in luminal accumulation of cholesterol. Moreover, trans-Golgi resident proteins mislocalize to endosomal compartments upon ORP5 depletion, which depends on a functional NPC1. Our results establish the first link between NPC1 and a cytoplasmic sterol carrier, and suggest that ORP5 may cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes.

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