Endocrine Abstracts

The lipid species that comprise cell membranes are not uniformly distributed. Instead different lipids can become organised into patches, or microdomains, in the membrane. These microdomains, often termed lipid rafts, can include or exclude proteins with the result that they present a locally different character compared to the surrounding membrane. Lipid rafts are enriched in cholesterol and glycosphingolipid; the saturated acyl chains of the sphingolipids promotes their dense packing in the membrane while cholesterol fills up the space between adjacent sphingolipid head groups and fatty acid chains. This dense packaging gives rise to the characteristic detergent resistance of lipid rafts and allows their simple biochemical purification and analysis. Following extraction of cells with cold detergent (such as Triton X-100) lipid rafts remain detergent insoluble and because of their high lipid content will float to an area of low density when subjected to sucrose gradient centrifugation. This allows the lipid rafts and associated proteins to be separated from other non-raft cellular components. Lipid rafts are proposed to play crucial roles in a number of diverse cellular processes including signalling in T-cells, exocytosis, GLUT4 translocation and assembly of viral particles. In addition, they are thought to play a prominent role in the sorting of proteins to the apical membrane in polarised epithelial cells, possibly in concert with other signals. Recently a number of regulated secretory proteins including PC2, PC1/3, CPE and thyroglobulin have been shown to become lipid raft-associated. Inhibition of lipid raft formation, by removal of cholesterol or inhibiting sphingolipid biosynthesis, has disrupted the intracellular localisation of some of these proteins leading to the proposal that lipid rafts also play a role in targeting to the regulated secretory pathway in neuroendocrine cells.