Comment on 'Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol'
- University of Ottawa, Canada
- St Michael's Hospital, Canada
- Weill Cornell Medical College, United States
Abstract
The plasma membrane in mammalian cells is rich in cholesterol. How cholesterol partitions between the two leaflets of the plasma membrane remains a matter of debate. Recently, Liu et al used domain 4 (D4) of perfringolysin O as a cholesterol sensor to argue that cholesterol is mostly in the exofacial leaflet (Liu et al., 2017). This conclusion was made by interpreting D4 binding in live cells using in vitro calibrations with liposomes. However, liposomes may be unfaithful in mimicking the plasma membrane, as we demonstrate here. Also, D4 binding is highly sensitive to the presence of cytosolic proteins. In addition, we find that a D4 variant, that requires >35 mol% cholesterol to bind to liposomes in vitro, does in fact bind to the cytoplasmic leaflet of the plasma membrane in a cholesterol-dependent manner. Thus, we believe, based on the current evidence, that it is unlikely that there is a significantly higher proportion of cholesterol in the exofacial leaflet of the plasma membrane compared to the cytosolic leaflet.
Data availability
All data generated or analysed during this study are included in the manuscript.
Article and author information
Author details
Frederick R Maxfield
Funding
Canadian Institutes of Health Research (Operating Grant MOP-130453)
- Xiaohui Zha
Natural Sciences and Engineering Research Council of Canada (Discovery Grant RGPIN 40210-2013)
- Xiaohui Zha
National Institutes of Health (R01 GM123462)
- Frederick R Maxfield
Canadian Institutes of Health Research (MOP-133656)
- Gregory D Fairn
The authors declare that there was no funding for this work
Copyright
© 2018, Courtney et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Comment on 'Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol'
eLife 7:e38493.
https://doi.org/10.7554/eLife.38493
