Heparan Sulphate Proteoglycan in Drosophila

描述（由申请人提供） 在脊椎动物和果蝇中，许多细胞间信号传导事件 已经证明需要一类细胞表面蛋白，硫酸乙酰肝素 蛋白聚糖（HSPG）。HSPG是具有修饰的连接链的蛋白质， 糖聚合物，称为硫酸乙酰肝素（HS）。核心蛋白和 HSPG's的HS链已被证明对于许多信号传导事件是重要的。 该计划的目标是：1）鉴定果蝇中的无效突变体 dally基因，其编码磷脂酰肌醇蛋白聚糖样HSPG的核心蛋白2）鉴定 抑制剂和增强剂的日常，将产生突变的HS 合成酶以及其他修饰剂，和3）确定的作用， 每一种鉴定的果蝇O-磺基转移酶（OST）在 利用RNA干扰的发育信号。几种遗传和分子 将使用测定来确定特定的突变或一种突变的减少是否是 OST的影响无翼，刺猬，FGF，或Decapentaplegic信号 途径。这些研究将极大地扩展我们对 HSPG的信号和发展。

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.