G Protein Signaling Crosstalk & Eukaryot Quorum Sensing

G 蛋白信号串扰

• 批准号: 6772191
• 负责人: DERRICK T BRAZILL
• 金额: $ 11.38万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772191
• 关键词: Dictyostelium; G protein; genetic screening; guanosinetriphosphatase activating protein; phospholipase D; protein kinase C; protein localization; protein protein interaction; protozoal genetics; quorum sensing

DESCRIPTION (provided by applicant): Quorum sensing, the ability of a cell to sense the density of neighboring cells, plays a vital role in eukaryotic processes ranging from organ formation and regeneration to disease progression in trypanosome infections. The social amoeba Dictyostelium discoideum is the simplest eukaryote to display quorum sensing, and due to its genetic tractability presents itself as an excellent organism in which to study this phenomenon. D. discoideum links its development to quorum sensing by using one G protein mediated signaling pathway to regulate a second G protein pathway. While G-protein signaling cross-talk is known to be critical for regulating neuronal function in mammals, this is the first example of such signaling being used in quorum sensing. In addition, the mammalian work is hindered by the lack of physiological models and the difficulties of genetics in the systems studied. Thus, the components that link one G protein signaling pathway with another remain unclear in both neurons and quorum sensing. The long-range goal of this research is to identify how organisms monitor and regulate the cell density of different tissues. The objective of this proposal is to further identify the components involved in G protein signaling cross-talk in quorum sensing in D. discoideum. The central hypothesis will be tested and the overall objective of this proposal will be accomplished by pursuing 5 specific aims. The aims are: 1) Determine whether OKC is required for quorum sensing, and if it is activated by translocation. 2) Determine the activity, cellular localization and binding partners of PldB during G protein cross-talk in quorum sensing. 3) Determine whether PLD is required for proper cellular differentiation. 4) Determine the epistatic relationship between PKC, PLD and RGS in G protein cross-talk 5) Identify other genes involved in G protein cross-talk in quorum sensing in a second site suppressor screen.

描述（由申请人提供）：法定感应，细胞感知相邻细胞密度的能力，在从器官形成和真核过程中起着至关重要的作用 锥虫感染中疾病进展的再生。社交变形虫dictyostelium Discoideum是显示法定感应的最简单的真核生物，并且由于其遗传性障碍性 将自己作为一种研究这种现象的优秀生物。 D. Discoideum通过使用一种G蛋白介导的信号传导途径来调节第二G蛋白途径，将其发育与法规传感联系起来。虽然已知G蛋白信号传导交叉对话对于调节哺乳动物的神经元功能至关重要，但这是在Quorum Sensing中使用此类信号的第一个例子。此外，在所研究系统中缺乏生理模型和遗传学的困难，哺乳动物的工作受到了阻碍。因此，在神经元和法定感应中，将一种G蛋白信号通路与另一个G蛋白信号通路连接起来的组件尚不清楚。 这项研究的远程目标是确定生物如何监测和调节不同组织的细胞密度。该提案的目的是进一步确定D. discoideum中群体传感中G蛋白信号传导串扰涉及的成分。将检验中心假设，该提案的总体目标将由 追求5个具体目标。目的是： 1）确定是否需要OKC来进行群体传感，以及是否通过易位激活。 2）确定Quorum感应中G蛋白串扰期间PLDB的活性，细胞定位和结合伴侣。 3）确定是否需要PLD才能适当的细胞分化。 4）确定G蛋白串扰中PKC，PLD和RGS之间的同义关系 5）在第二个位点抑制器筛选中，确定在群体传感中涉及G蛋白串扰的其他基因。