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Sterol transfer, PI 4P consumption, and control of membrane lipid order by endogenous OSBP
Author(s) -
Mesmin Bruno,
Bigay Joëlle,
Polidori Joël,
Jamecna Denisa,
LacasGervais Sandra,
Antonny Bruno
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201796687
Subject(s) - biology , membrane contact site , lipid droplet , microbiology and biotechnology , endoplasmic reticulum , plant lipid transfer proteins , golgi apparatus , organelle , lipid microdomain , biochemistry , membrane protein , integral membrane protein , membrane , gene
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/ PI 4P 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 PI 4P 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 PI 4P, a consumption that depends on the amount of cholesterol to be transported. Inhibiting the spatially restricted PI 4‐kinase PI 4 KIII β triggers large periodic traveling waves of PI 4P across the TGN . These waves are cadenced by long‐range PI 4P production by PI 4 KII α and PI 4P consumption by OSBP . Collectively, these data indicate a massive spatiotemporal coupling between cholesterol transport and PI 4P turnover via OSBP and PI 4‐kinases to control the lipid composition of subcellular membranes.