G PROTEINS IN THE CNS

G蛋白将大量第一信使的受体偶联到 各种第二信使系统，产生不同的生物 效果。在体内对这些分子的研究仅限于细胞。 培养系统和病理条件的描述 改变G蛋白的水平或功能。系统当前不支持 这些分子在复杂生物中的作用是不存在的 可以以系统的方式处理流程。我们打算分析 果蝇体内G蛋白在这些过程中的作用。 初步研究涉及G蛋白的特征 苍蝇成虫中枢神经系统的存在及蝇头cDNA的分离 编码蛋白质的文库，这些蛋白质与每个主要的 脊椎动物表达的G蛋白A亚基的类别。我们将延长 这些研究通过分离和鉴定编码这些基因的基因 用于确定其生产替代物的潜力的cDNA 成绩单。将产生针对每一种的特定多肽的抗体 为我们提供了检查Gα亚单位的工具 各蛋白质在神经系统中的分布和表达 发展。我们将尝试确定功能同调 在类似苍蝇的克隆和脊椎动物的等价物之间 评估苍蝇cDNA对该蛋白的补充能力 S49细胞存在缺陷。几个孩子的母性表达 Fly G蛋白α亚基将被操纵以评估其作用 这些蛋白质在神经系统发育的早期。使用 在果蝇中可用的遗传工具，我们将尝试分离 取消Fly Gα亚基表达的突变。是这样的 突变本身将被研究，并为我们提供 表达G蛋白α亚单位基因的受体菌株 哪些已经在体外被改变，购买位点特异性突变和其他 方法：研究方法。使用我们将建立的系统，G蛋白将被用于 第一次，通过一些综合方法进行研究， 以确定它们在神经系统功能中所起的作用 发展。

G proteins couple the receptors for a vast array of first messengers to a variety of second messenger systems which generate diverse biological effects. The study of these molecules in vivo has been limited to cell culture systems and the description of pathological conditions which alter the level or function of G proteins. A system does not currently exist ni which the role of these molecules in complex biological processes can be addressed in a systematic way. We intend to analyze the role of G proteins in these processes in the fruit fly, Drosophila. Preliminary studies have involved the characterization of the G proteins present in the adult fly CNS and the isolation of cDNAs from fly head libraries which code for proteins highly homologous to each of the main classes of G protein a subunit expressed in vertebrates. We will extend these studies by isolating and characterizing the genes coding for these cDNAs to determine their potential for the production of alternate transcripts. Antibodies will be generated to peptides specific for each of the G alpha subunit protein to provide us with tools to examine the distribution and expression of each protein during nervous system development. We will attempt to determine the functional homology between fly Gs alpha-like clones and the vertebrate equivalents by assessing the ability of fly cDNAs for this protein to complement the defect present in S49 cyc- cells. The maternal expression of several of the fly G protein alpha subunits will be manipulated to assess the role of these proteins in the early nervous system development. Using the genetic tools available in Drosophila, we will attempt to isolate mutations which abolish the expression of fly G alpha subunits. Such mutations will be studied in their own right and provide us with recipient strains in which to express G protein alpha subunit genes which have been altered in vitro buy site specific mutagenesis and other methods. Using the system we will establish, G proteins will be, for the first time, subjected to study by a number of combined approaches in vivo to determine the role they play in nervous system function and development.