Submitted on February 20, 2008
Revised on April 9, 2008
Accepted on April 21, 2008
Lipid composition of microdomains is altered in a cell model of Gaucher disease
Leanne K. Hein, Stephen Duplock, John J. Hopwood, and Maria Fuller
Genetic Medicine, Children, Youth and Women's Health Service, North Adelaide, South Australia 5006
Corresponding Author: maria.fuller{at}adelaide.edu.au
The formation of cholesterol and sphingolipids into specialised 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 solubilisation in non-ionic detergents enabling them to be isolated as detergent resistant membranes (DRM). In this study we characterised 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, di-, 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 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.
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