Heparan Sulphate Proteoglycan in Drosophila

描述(由申请人提供) 脊椎动物和果蝇中的许多细胞间信号事件都有 已被证明需要一类细胞表面蛋白，硫酸乙酰肝素 蛋白多糖(HSPG‘s)。HSPG是带有修饰链的蛋白质 糖类聚合物，称为硫酸乙酰肝素(HS)。核心蛋白和 HSPG的HS链已经被证明在许多信号事件中是重要的。 这项提议的目标是1)在果蝇中识别零突变体 Dally基因，它编码了一种类似于海豚的HSPG的核心蛋白 将在HS中产生突变的DAILE的抑制和增强子 合成酶以及其他修饰剂，以及3)确定 已鉴定的果蝇O-硫酸盐转移酶(OST)中的每一个都参与了 使用RNA干扰的发育信号。几种遗传和分子 化验将被用来确定一个特定的突变或减少 OST的影响无翼、刺猬、成纤维细胞生长因子或十字麻痹信号 小路。这些研究将极大地扩大我们对 HSPG在信号和开发方面。

DESCRIPTION (provided by applicant) Many intercellular signaling events in both vertebrates and in Drosophila have been shown to require one class of cell surface proteins, the heparan sulphate proteoglycans (HSPG's). HSPG's are proteins with attached chains of modified sugars polymers, called heparan sulphate (HS). Both the core proteins and the HS chains of HSPG's have been shown to be important for many signaling events. The goals of this proposal are to 1) identify null mutants in the Drosophila dally gene, which encodes the core protein of a glypican-like HSPG 2) identify suppressors and enhancers of daily that will yield mutations in the HS synthetic enzymes as well as other modifiers, and 3) ascertain the role that each of the identified Drosophila O-sulphotransferases (OST) plays in developmental signaling using RNA interference. Several genetic and molecular assays will be used to determine if a particular mutation or reduction of one of the OST's affects the Wingless, Hedgehog, FGF, or Decapentaplegic signaling pathways. These studies will greatly expand our understanding of the roles of HSPG's in signaling and development.