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

描述(申请人提供)：异三聚体G蛋白是一种重要的双分子开关，它从一系列不同的膜受体为神经递质、激素和细胞外形态原传递信号，以激活下游的细胞内信号通路。G？12/13家族的成员在胚胎发育过程中特别重要，因为它们对循环系统的发育是必不可少的，对胚胎血管生成也是必需的。这项建议的目的是了解Ric-8如何参与G？12/13途径的信号传递。我们将以果蝇原肠发育途径为模型系统来研究Ric-8，以利用强大的细胞生物学工具和对果蝇G？12/13信号通路的丰富理解。在这个提案中，我们将1)在G？12/13信号的背景下进行Ric-8的结构-功能研究；2)识别调节果蝇Ric-8活性所需的新蛋白质。鉴于果蝇和人类之间这些通路的HIH保守程度，这些研究将有助于了解G？12/13蛋白信号在血管发育过程中的调节，并将发现在调节血管生成方面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.