Format

Send to

Choose Destination
EMBO J. 2017 Nov 2;36(21):3156-3174. doi: 10.15252/embj.201796687. Epub 2017 Oct 4.

Sterol transfer, PI4P consumption, and control of membrane lipid order by endogenous OSBP.

Author information

1
Université Côte d'Azur, Inserm, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
2
Université Côte d'Azur, Centre Commun de Microscopie Appliquée, Nice, France.
3
Université Côte d'Azur, Inserm, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France antonny@ipmc.cnrs.fr.

Abstract

The network of proteins that orchestrate the distribution of cholesterol among cellular organelles is not fully characterized. We previously proposed that oxysterol-binding protein (OSBP) drives cholesterol/PI4P exchange at contact sites between the endoplasmic reticulum (ER) and the trans-Golgi network (TGN). Using the inhibitor OSW-1, we report here that the sole activity of endogenous OSBP makes a major contribution to cholesterol distribution, lipid order, and PI4P turnover in living cells. Blocking OSBP causes accumulation of sterols at ER/lipid droplets at the expense of TGN, thereby reducing the gradient of lipid order along the secretory pathway. OSBP consumes about half of the total cellular pool of PI4P, a consumption that depends on the amount of cholesterol to be transported. Inhibiting the spatially restricted PI4-kinase PI4KIIIβ triggers large periodic traveling waves of PI4P across the TGN These waves are cadenced by long-range PI4P production by PI4KIIα and PI4P consumption by OSBP Collectively, these data indicate a massive spatiotemporal coupling between cholesterol transport and PI4P turnover via OSBP and PI4-kinases to control the lipid composition of subcellular membranes.

KEYWORDS:

Golgi apparatus; cholesterol; lipid‐transfer protein; membrane contact site; phosphatidylinositol 4‐phosphate

PMID:
28978670
PMCID:
PMC5666618
DOI:
10.15252/embj.201796687
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center