Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins
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Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins. / 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.
In: Cell, Vol. 161, No. 3, 23.04.2015, p. 581-594.Research output: Contribution to journal › Article › Scientific › peer-review
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TY - JOUR
T1 - Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins
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.
UR - http://www.scopus.com/inward/record.url?scp=84928392356&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.03.048
DO - 10.1016/j.cell.2015.03.048
M3 - Article
VL - 161
SP - 581
EP - 594
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -