Transbilayer Lipid Interactions Mediate Nanoclustering of Lipid-Anchored Proteins

Panda, Aniruddha (2015) Transbilayer Lipid Interactions Mediate Nanoclustering of Lipid-Anchored Proteins. Cell, 161. pp. 581-594.

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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 cholesteroldependent 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-chaincontaining phosphatidylserine (PS) is necessary for transbilayer coupling. All- tom 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.

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 17 Apr 2019 09:23
Last Modified: 17 Apr 2019 09:23

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