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

Article Article scientifique Article Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology eng 2009 author Guan Xue Li author Souza Cleiton author Pichler Harald author Dewhurst Gisele 108437 author Schaad Olivier 0000-0003-1576-783X 23118 author Kajiwara Kentaro author Wakabayashi Hirotomo author Ivanova Tanya 666474 author Castillon Guillaume Alain 560227 author Piccolis Manuele 648075 author Abe Fumiyoshi author Loewith Robbie Joséph 630703 author Funato Kouichi author Wenk Markus R author Riezman Howard 134430 2083-2095 10.1091/mbc.E08-11-1126 19225153 1059-1524 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. Anisotropy Biological Transport/drug effects Caffeine/pharmacology Cell Membrane/drug effects/physiology Cluster Analysis Gene Expression Profiling Mutation/genetics Phenotype Saccharomyces cerevisiae/cytology/drug effects/genetics/physiology Saccharomyces cerevisiae Proteins/metabolism Sirolimus/pharmacology Sorbic Acid/pharmacology Sphingolipids/chemistry/metabolism Sterols/biosynthesis/chemistry/metabolism Dewey 570 43 Département de biologie moléculaire 161 false Molecular biology of the cell 20 7 4cb61489-66aa-49fc-9b6d-cd8498ab788d Article (Published version) Public zmk2083.pdf 596018 application/pdf openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology	Molecular biology of the cell			2009	757	691

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Ivanova, Tanya