Understanding the role of Ric-8 in Ga 12/13 signaling

描述（由申请人提供）：异源三聚体G蛋白是重要的双分子开关，其从神经递质、激素和细胞外形态发生素的多种膜受体传递信号，以激活下游细胞内信号传导途径。G的成员？12/13家族在胚胎发育过程中特别重要，因为它们对循环系统的发育至关重要，并且是胚胎血管生成所需的。该提案的目标是了解Ric-8如何参与G？12/13路径。我们将利用果蝇原肠胚形成通路作为研究Ric-8的模型系统，利用强大的细胞生物学工具和丰富的了解G？12/13信号通路。在本研究中，我们将1）在G？12/13信号传导;和2）鉴定调节果蝇中Ric-8活性所需的新蛋白。鉴于苍蝇和人类之间的这些途径的高度保守，这些研究将提供G？12/13蛋白信号转导在血管发育过程中，并将确定新的分子与潜在的治疗重要性，在调节血管生成。

DESCRIPTION (provided by applicant): Heterotrimeric G proteins are important bi-molecular switches that transmit signals from a diverse array of membrane receptors for neurotransmitters, hormones and extracellular morphogens to activate downstream intracellular signaling pathways. Members of the G?12/13 family are particularly important during embryonic development as they are essential for the development of the circulatory system and are required for embryonic angiogenesis. The goal of this proposal is to understand how Ric-8 participates in signaling in the G?12/13 pathway. We will use the Drosophila gastrulation pathway as a model system to study Ric-8 to take advantage of the powerful cell biological tools and rich understanding of the G?12/13 signaling pathway in flies. In this proposal we will 1) Conduct a structure-function study of Ric-8 within the context of G?12/13 signaling; and 2) Identify novel proteins that are required for regulating Ric-8 activity in Drosophila. Given the hih degree of conservation of these pathways between flies and humans, these studies will provide understanding of the regulation of G?12/13 protein signaling during vascular development and will identify novel molecules with potential therapeutic importance in the regulation of angiogenesis.