Molecular dissection of organization and dynamics of membrane lipid domains

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Whereas the bilayer organization of biomembranes can be reconstituted in artificial liposomes with a simple lipid composition, biological membranes contain thousands of different lipid species, whose cellular distribution is stringently controlled. This complex distribution of lipids suggests that the targeting of lipids is highly regulated and that cells require a complex lipid supramolecular organization within their membranes. Our aim is to understand the organization, assembly and function of specific lipids and lipid domains. For this purpose, we developed several lipid-specific probes and a new inhibitor of Sphingolipid biosynthesis. These tools, in conjunction with biochemical, biophysical and cell biological approaches are now starting to provide valuable information to understand lipid supramolecular organization. Application of our probes uncovered several aspects of cellular lipid organization. Major subjects performed during these three years are :1.Characterization of sphingomyelin-specific toxin, lysenin2.Studies on organization and dynamics of sphingomyelin3.Characterization of sulfamisterin (AB5366), a new inhibitor of serine palmitoyltransferase4.Studies on distribution and transport of cholesterol-rich membrane domains5.Cellular distribution of phosphatidylethanolamine in yeast