TitleTransbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins.
Publication TypeJournal Article
Year of Publication2015
AuthorsRaghupathy 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 Published2015 Apr 23
KeywordsActins, 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.

Alternate JournalCell
PubMed ID25910209
PubMed Central IDPMC4651428
Grant ListGM090270 / GM / NIGMS NIH HHS / United States
R01 GM090270 / GM / NIGMS NIH HHS / United States