Format

Send to

Choose Destination
Cell. 2015 Apr 23;161(3):581-594. doi: 10.1016/j.cell.2015.03.048.

Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins.

Author information

1
National Centre for Biological Sciences (TIFR), Bellary Road, Bangalore 560 065, India; Shanmugha Arts, Science, Technology & Research Academy, Thanjavur 613401, India.
2
Raman Research Institute, C.V. Raman Avenue, Bangalore 560 080, India; Tampere University of Technology, Korkeakoulunkatu 10, 33720 Tampere, Finland.
3
Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
4
Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA.
5
National Centre for Biological Sciences (TIFR), Bellary Road, Bangalore 560 065, India; Manipal University, Madhav Nagar, Manipal 576104, Karnataka, India.
6
National Centre for Biological Sciences (TIFR), Bellary Road, Bangalore 560 065, India; Raman Research Institute, C.V. Raman Avenue, Bangalore 560 080, India. Electronic address: madan@ncbs.res.in.
7
National Centre for Biological Sciences (TIFR), Bellary Road, Bangalore 560 065, India; Institute for Stem Cell Biology and Regenerative Medicine, Bellary Road, Bangalore 560 065, India. Electronic address: mayor@ncbs.res.in.

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.

PMID:
25910209
PMCID:
PMC4651428
DOI:
10.1016/j.cell.2015.03.048
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center