Lipid-regulated Sterol Transfer Between Closely Apposed Membranes by Oxysterol-binding Protein Homologues

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2009 Dec 17

PMID 20008566

Citations 108

Authors

Timothy A Schulz

Mal-Gi Choi

Sumana Raychaudhuri

Jason A Mears

Rodolfo Ghirlando

Jenny E Hinshaw

William A Prinz

Affiliations

Soon will be listed here.

Abstract

Sterols are transferred between cellular membranes by vesicular and poorly understood nonvesicular pathways. Oxysterol-binding protein-related proteins (ORPs) have been implicated in sterol sensing and nonvesicular transport. In this study, we show that yeast ORPs use a novel mechanism that allows regulated sterol transfer between closely apposed membranes, such as organelle contact sites. We find that the core lipid-binding domain found in all ORPs can simultaneously bind two membranes. Using Osh4p/Kes1p as a representative ORP, we show that ORPs have at least two membrane-binding surfaces; one near the mouth of the sterol-binding pocket and a distal site that can bind a second membrane. The distal site is required for the protein to function in cells and, remarkably, regulates the rate at which Osh4p extracts and delivers sterols in a phosphoinositide-dependent manner. Together, these findings suggest a new model of how ORPs could sense and regulate the lipid composition of adjacent membranes.

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