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


Guan, Xue Li; Souza, Cleiton M; Pichler, Harald; Dewhurst, Gisèle; Schaad, Olivier; Kajiwara, Kentaro; Wakabayashi, Hirotomo; Ivanova, Tanya; Castillon, Guillaume A; Piccolis, Manuele; Abe, Fumiyoshi; Loewith, Robbie; Funato, Kouichi; Wenk, Markus R; Riezman, Howard (2009). Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Molecular Biology of the Cell, 20(7):2083-95.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > LipidX
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2009
Deposited On:01 Jul 2013 09:52
Last Modified:07 Dec 2017 21:31
Publisher:American Society for Cell Biology
ISSN:1059-1524
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1091/mbc.E08-11-1126
PubMed ID:19225153

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