Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins

Riya Raghupathy; Anupama Ambika Anilkumar; Anirban Polley; Parvinder Pal Singh; Mahipal Yadav; Charles Johnson; Sharad Suryawanshi; Varma Saikam; Sanghapal D. Sawant; Aniruddha Panda; Zhongwu Guo; Ram A. Vishwakarma; Madan Rao; Satyajit Mayor

doi:10.1016/j.cell.2015.03.048

Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins

Riya Raghupathy, Anupama Ambika Anilkumar, Anirban Polley, Parvinder Pal Singh, Mahipal Yadav, Charles Johnson, Sharad Suryawanshi, Varma Saikam, Sanghapal D. Sawant, Aniruddha Panda, Zhongwu Guo, Ram A. Vishwakarma, Madan Rao, Satyajit Mayor

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177 Citations (Scopus)

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.

Original language	English
Pages (from-to)	581-594
Number of pages	14
Journal	Cell
Volume	161
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2015.03.048
Publication status	Published - 23 Apr 2015
Publication type	A1 Journal article-refereed

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Publication forum level 3

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Medicine(all)

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10.1016/j.cell.2015.03.048

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title = "Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins",

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.",

author = "Riya Raghupathy and Anilkumar, {Anupama Ambika} and Anirban Polley and Singh, {Parvinder Pal} and Mahipal Yadav and Charles Johnson and Sharad Suryawanshi and Varma Saikam and Sawant, {Sanghapal D.} and Aniruddha Panda and Zhongwu Guo and Vishwakarma, {Ram A.} and Madan Rao and Satyajit Mayor",

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AU - Raghupathy, Riya

AU - Anilkumar, Anupama Ambika

AU - Polley, Anirban

AU - Singh, Parvinder Pal

AU - Yadav, Mahipal

AU - Johnson, Charles

AU - Suryawanshi, Sharad

AU - Saikam, Varma

AU - Sawant, Sanghapal D.

AU - Panda, Aniruddha

AU - Guo, Zhongwu

AU - Vishwakarma, Ram A.

AU - Rao, Madan

AU - Mayor, Satyajit

PY - 2015/4/23

Y1 - 2015/4/23

N2 - 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.

AB - 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.

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Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins

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