Abstrakti
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.
Alkuperäiskieli | Englanti |
---|---|
Sivut | 581-594 |
Sivumäärä | 14 |
Julkaisu | Cell |
Vuosikerta | 161 |
Numero | 3 |
DOI - pysyväislinkit | |
Tila | Julkaistu - 23 huhtik. 2015 |
OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä |
Julkaisufoorumi-taso
- Jufo-taso 3
!!ASJC Scopus subject areas
- Yleinen biokemia, genetiikka ja molekyylibiologia
- Yleinen lääketiede