Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins.
|Title||Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Raghupathy R, Anilkumar AAmbika, Polley A, Singh PPal, Yadav M, Johnson C, Suryawanshi S, Saikam V, Sawant SD, Panda A, Guo Z, Vishwakarma RA, Rao M, Mayor S|
|Date Published||2015 Apr 23|
|Keywords||Actins, Animals, Cell Membrane, CHO Cells, Cricetulus, Glycosylphosphatidylinositols, Lipid-Linked Proteins, Molecular Dynamics Simulation, Phosphatidylserines|
Understanding how functional lipid domains in live cell membranes are generated has posed a challenge. Here, we show that transbilayer interactions are necessary for the generation of cholesterol-dependent nanoclusters of GPI-anchored proteins mediated by membrane-adjacent dynamic actin filaments. We find that long saturated acyl-chains are required for forming GPI-anchor nanoclusters. Simultaneously, at the inner leaflet, long acyl-chain-containing phosphatidylserine (PS) is necessary for transbilayer coupling. All-atom molecular dynamics simulations of asymmetric multicomponent-membrane bilayers in a mixed phase provide evidence that immobilization of long saturated acyl-chain lipids at either leaflet stabilizes cholesterol-dependent transbilayer interactions forming local domains with characteristics similar to a liquid-ordered (lo) phase. This is verified by experiments wherein immobilization of long acyl-chain lipids at one leaflet effects transbilayer interactions of corresponding lipids at the opposite leaflet. This suggests a general mechanism for the generation and stabilization of nanoscale cholesterol-dependent and actin-mediated lipid clusters in live cell membranes.
|PubMed Central ID||PMC4651428|
|Grant List||GM090270 / GM / NIGMS NIH HHS / United States |
R01 GM090270 / GM / NIGMS NIH HHS / United States