| Literature DB >> 25910209 |
Riya Raghupathy1, Anupama Ambika Anilkumar1, Anirban Polley2, Parvinder Pal Singh3, Mahipal Yadav3, Charles Johnson4, Sharad Suryawanshi4, Varma Saikam3, Sanghapal D Sawant3, Aniruddha Panda5, Zhongwu Guo4, Ram A Vishwakarma3, Madan Rao6, Satyajit Mayor7.
Abstract
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.Entities:
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Year: 2015 PMID： 25910209 PMCID： PMC4651428 DOI： 10.1016/j.cell.2015.03.048
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582