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- W1964738976 abstract "Lateral membrane microdomains, or lipid rafts, are considered fundamental to a wide range of biological processes. The association of cholesterol and sphingolipids promotes transient, nanoscopic protein-protein interactions that enhance membrane signal transduction. In giant unilamellar vesicles (GUVs) or giant plasma membrane vesicles (GPMVs), these microdomains are readily resolvable by optical microscopy. However, similar visible microdomains have not been observed in living cells, which has been a long-standing mystery. A unique feature of the native plasma membrane is the high degree of transbilayer lipid asymmetry and, particularly, with long acyl chain sphingolipids exclusively in the outer leaflet. The impact of asymmetry on optically resolvable microdomains is not known, nor is the role of long acyl chain sphingomyelin (SM). Here, we show that GUVs fail to form visible microdomains if long acyl chain SM is exclusively in the outer leaflet but, if long acyl chain SM is placed in both leaflets, GUVs readily produce visible microdomains. With a novel methodology capable of analyzing cholesterol in the individual leaflets, we obtained evidence that long acyl chain SM, not short acyl chain SM, drives cholesterol into the inner-leaflet of large unilamellar vesicles. This depletes cholesterol from the outer leaflet, thereby providing a mechanism for abolishing visible microdomains. We finally confirm that, in native plasma membrane - human erythrocytes, the majority of cholesterol is indeed in the inner leaflet. We conclude that native plasma membrane cannot form visible microdomains, primarily due to lack of cholesterol in the outer leaflet as the consequence of exofacial long acyl SM. Our findings therefore resolve the long-standing puzzle and uncover a novel fundamental organization principle for the plasma membrane." @default.
- W1964738976 created "2016-06-24" @default.
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- W1964738976 date "2015-01-01" @default.
- W1964738976 modified "2023-09-27" @default.
- W1964738976 title "Long acyl Chain Sphingolipids Govern Visible Microdomains and Cholesterol in Both Model and Plasma Membranes" @default.
- W1964738976 doi "https://doi.org/10.1016/j.bpj.2014.11.200" @default.
- W1964738976 hasPublicationYear "2015" @default.
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