Lipid composition of microdomains is altered in a cell model of Gaucher disease*

Journal of Lipid Research

Maria Fuller¹  Leanne K. Hein²  Stephen Duplock²  John J. Hopwood² 

[1] Department of Pediatrics, University of Adelaide, Adelaide, South Australia 5005;Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children, Youth and Women's Health Service, North Adelaide, South Australia 5006;

关键词: membrane rafts;    detergent-resistant membranes;    mass spectrometry;    glucosylceramide;    lysosomal storage disorder;    sphingolipids;   

DOI  :  

来源: DOAJ

【 摘 要 】

The formation of cholesterol and sphingolipids into specialized liquid-ordered membrane microdomains (rafts) has been proposed to function in the intracellular sorting and transport of proteins and lipids. Defined by biochemical criteria, rafts resist solubilization in nonionic detergents, enabling them to be isolated as detergent-resistant membranes (DRM). In this study, we characterized the lipid composition of DRM from a cell model of the sphingolipid storage disorder, Gaucher disease, in which the catabolism of the sphingolipid glucosylceramide (GC) is impaired. In this cell model, we showed that GC accumulated primarily in the DRM, with smaller secondary increases in ceramide, dihexosylceramide, trihexosylceramide, and phosphatidylglycerol. This suggested that not only was lipid metabolism altered as a consequence of the cells' inability to degrade GC, but this affected the DRM rather than other regions of the membrane. This increase in lipids in the DRM may be responsible for the altered lipid and protein sorting seen in Gaucher disease. Analysis of individual lipid species revealed preservation of the shorter and fully saturated fatty acid species in the DRM, suggesting that the highly ordered and tightly packed nature of the DRM is maintained.

【 授权许可】

Unknown