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Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins

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. W...

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Published in:Cell 2015-04, Vol.161 (3), p.581-594
Main Authors: Raghupathy, Riya, Anilkumar, Anupama Ambika, Polley, Anirban, Singh, Parvinder Pal, Yadav, Mahipal, Johnson, Charles, Suryawanshi, Sharad, Saikam, Varma, Sawant, Sanghapal D, Panda, Aniruddha, Guo, Zhongwu, Vishwakarma, Ram A, Rao, Madan, Mayor, Satyajit
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Language:English
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2015.03.048