Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol.

Abstract:

:Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed marked transbilayer asymmetry of PM cholesterol (TAPMC) in various mammalian cells, with the concentration in the inner leaflet (IPM) being ∼12-fold lower than that in the outer leaflet (OPM). The asymmetry was maintained by active transport of cholesterol from IPM to OPM and its chemical retention at OPM. Furthermore, the increase in the IPM cholesterol level was triggered in a stimulus-specific manner, allowing cholesterol to serve as a signaling lipid. We found excellent correlation between the IPM cholesterol level and cellular Wnt signaling activity, suggesting that TAPMC and stimulus-induced PM cholesterol redistribution are crucial for tight regulation of cellular processes under physiological conditions.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Liu SL,Sheng R,Jung JH,Wang L,Stec E,O'Connor MJ,Song S,Bikkavilli RK,Winn RA,Lee D,Baek K,Ueda K,Levitan I,Kim KP,Cho W

doi

10.1038/nchembio.2268

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

268-274

issue

3

eissn

1552-4450

issn

1552-4469

pii

nchembio.2268

journal_volume

13

pub_type

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