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 Bioljournal_title
Nature chemical biologyauthors
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 Wdoi
10.1038/nchembio.2268subject
Has Abstractpub_date
2017-03-01 00:00:00pages
268-274issue
3eissn
1552-4450issn
1552-4469pii
nchembio.2268journal_volume
13pub_type
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