Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol
Orthogonal cholesterol sensors that are useful for imaging cholesterol in the plasma membrane leaflets reveal an asymmetry in which a high outer leaflet concentration is important for signaling processes and is potentially actively maintained. Controlled distribution of lipids across various cell me...
Saved in:
Published in | Nature chemical biology Vol. 13; no. 3; pp. 268 - 274 |
---|---|
Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.03.2017
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Orthogonal cholesterol sensors that are useful for imaging cholesterol in the plasma membrane leaflets reveal an asymmetry in which a high outer leaflet concentration is important for signaling processes and is potentially actively maintained.
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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 1552-4450 1552-4469 |
DOI: | 10.1038/nchembio.2268 |