Molecular dissection of organization and dynamics of membrane lipid domains

尽管生物膜的双层组织可以用简单的脂质组成在人工脂质体中重构，但生物膜含有数千种不同的脂质物质，其细胞分布受到严格控制。脂质的这种复杂分布表明，脂质的靶向是高度调节的，并且细胞在其膜内需要复杂的脂质超分子组织。我们的目标是了解特定脂质和脂质结构域的组织，组装和功能。为此，我们开发了几种脂质特异性探针和一种新的鞘脂生物合成抑制剂。这些工具，结合生物化学，生物物理和细胞生物学方法，现在开始提供有价值的信息，了解脂质超分子组织。我们的探针的应用揭示了细胞脂质组织的几个方面。主要研究内容有：1.鞘磷脂特异性毒素Lysenin的特性2.鞘磷脂的结构和动力学研究3.丝氨酸棕榈酰转移酶抑制剂磺胺酯（AB 5366）的特性4.富含胆固醇的膜结构域的分布和转运研究5.磷脂酰乙醇胺在酵母细胞中的分布

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