Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Biol Cell. 2009 Apr;20(7):2083-95. doi: 10.1091/mbc.E08-11-1126. Epub 2009 Feb 18.

Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology.

Author information

  • 1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.

Abstract

Sterols and sphingolipids are limited to eukaryotic cells, and their interaction has been proposed to favor formation of lipid microdomains. Although there is abundant biophysical evidence demonstrating their interaction in simple systems, convincing evidence is lacking to show that they function together in cells. Using lipid analysis by mass spectrometry and a genetic approach on mutants in sterol metabolism, we show that cells adjust their membrane composition in response to mutant sterol structures preferentially by changing their sphingolipid composition. Systematic combination of mutations in sterol biosynthesis with mutants in sphingolipid hydroxylation and head group turnover give a large number of synthetic and suppression phenotypes. Our unbiased approach provides compelling evidence that sterols and sphingolipids function together in cells. We were not able to correlate any cellular phenotype we measured with plasma membrane fluidity as measured using fluorescence anisotropy. This questions whether the increase in liquid order phases that can be induced by sterol-sphingolipid interactions plays an important role in cells. Our data revealing that cells have a mechanism to sense the quality of their membrane sterol composition has led us to suggest that proteins might recognize sterol-sphingolipid complexes and to hypothesize the coevolution of sterols and sphingolipids.

Comment in

PMID:
19225153
[PubMed - indexed for MEDLINE]
PMCID:
PMC2663937
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk