Hoch ungesättigte Sphingolipide: Biosynthese Expression und biologische Funktion während der Spermatogenese

与胆固醇和磷脂（包括鞘磷脂）不同，鞘脂糖（GSLs）是在哺乳动物细胞中特异性表达的细胞类型和分化阶段，含有几乎完全饱和的脂肪酸残基。不仅gsl的糖头基团，而且它们的膜锚点，即包括n -连接的脂肪酰基链在内的神经酰胺部分也显示出细胞类型特异性模式（Kolter和Sandhoff， 1999）。在我们之前的工作中，我们在小鼠睾丸中发现了一类新的GSLs（小鼠中有8个成员），具有结构特征，并在一定程度上具有组织学定位。它们被定义为一个新的类别，因为这些聚焦型GSLs （FGSLs）几乎完全含有多不饱和（多烯，4-6双键）超长链（C28-C32）脂肪酰基（VLCFA）残基（Sandhoff等人，2005）。缺乏神经节系列GSLs的小鼠也缺乏这种新型睾丸多细胞FGSLs。这类小鼠的精子发生被阻止在未成熟的圆形精子阶段，导致雄性不育（Takamiya et al., 1998）。本项目旨在了解这类新型多不饱和鞘脂的生物合成、定位和生物学功能。本项目的预期成果，除了拓展本领域的基础知识外，还有助于深入了解男性不育的可能原因。此外，它们还可能为男性避孕开辟新的领域。

In contrast to cholesterol and phospholipids including sphingomyelin, glycosphingolipids (GSLs) are cell type and differentiation stage specifically expressed in mammalian cells and contain almost exclusively saturated fatty acid residues. Not only the sugar head groups of GSLs but also their membrane anchors, i.e. the ceramide moieties including the N-linked fatty acyl chain show a cell type specific pattern (Kolter and Sandhoff, 1999). In our previous work we discovered in mouse testis, structurally characterized and to some extent histologically localized, a novel class of GSLs (8 members in mice). They were defined as a novel class because these fucosylated GSLs (FGSLs) contain almost exclusively polyunsaturated (polyenoic, 4-6 double bonds) very long chain (C28-C32) fatty acyl (VLCFA) residues (Sandhoff et al., 2005). Mice lacking ganglio-series GSLs are also deficient in this novel type of testicular polyenoic FGSLs. Spermatogenesis of such mice is arrested at the stage of immature round spermatids with the consequence of male infertility (Takamiya et al., 1998). The aim of this project is to understand the biosynthesis, localization and biological function of this novel class of polyunsaturated sphingolipids. Besides expanding the basic knowledge in this field, the expected results of this project may help to gain deeper insight into the possible causes of male infertility. They may, in addition, open new fields for male contraception.