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

描述（由申请人提供）：异三聚体G蛋白是重要的双分子开关，可传递来自神经递质、激素和细胞外形态因子的多种膜受体的信号，以激活下游细胞内信号通路。G？12/13家族在胚胎发育过程中尤为重要，因为它们对循环系统的发育至关重要，也是胚胎血管生成所必需的。本提案的目标是了解ric8如何参与G？12/13的途径。我们将以果蝇原肠形成通路为模型系统，利用强大的细胞生物学工具和对G？果蝇的12/13信号通路。在本提案中，我们将1)在G？12/13的信号;2)鉴定果蝇中调节ric8活性所需的新蛋白。鉴于果蝇和人类之间这些通路的高度保守性，这些研究将提供对G？研究血管发育过程中的12/13蛋白信号，并将发现在血管生成调控中具有潜在治疗意义的新分子。

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.