G Protein Activation through Uncoupling Regulator of G Signaling Protein, AtRGS1

通过 G 信号蛋白解偶联调节因子 AtRGS1 激活 G 蛋白

• 批准号: 1158054
• 负责人: Alan Jones
• 金额: $ 121.83万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1158054&HistoricalAwards=false
• 关键词: Protein; Activation; through; Uncoupling; Regulator

Intellectual Merit: For organisms to develop normally and to react appropriately to their environment, the cells that compose organisms must communicate with each other. Signals used by cells to communicate can be hormones, light, small molecules, electrical impulses, and touch. For example, light can turn on (activate) a light receptor which then activates a few other molecular complexes that then activates many more switches, and so on to afford changes in the cell. Between the signal at the receptor and the changes occurring in the cell is a molecular switch called the heterotrimeric G protein complex. Heterotrimeric G protein-coupled signaling is used for normal development of the organism as well as reactions to pathogens causing disease. Recent investigations of heterotrimeric G protein-coupled signaling using divergent model systems reveals a potential paradigm shift on how signal activation can be regulated. For example, in metazoans and fungi, activation is the rate limiting step and is catalyzed by a ligand-stimulated, cell surface G protein coupled receptor (GPCR). In contrast, plants regulate the back reaction which is GTP hydrolysis leading to the resting state, and in Arabidopsis, this resting state is maintained by a transmembrane regulator of G Signaling (RGS) protein designated AtRGS1. In Arabidopsis, D-glucose and/or sugar metabolites are signals that are mediated in part by the heterotrimeric G protein complex. It is hypothesized that glucose and/or sugar metabolites activate the G protein pathway by regulating the coupling between AtRGS1 and AtGPA1, and it has been demonstrated that D-glucose induces a rapid internalization of AtRGS1, but not AtGPA1. Key questions to be answered include how uncoupling is achieved, the consequence of uncoupling, and the molecular mechanism for uncoupling. These questions will be examined using mathematical modeling, genetic manipulation of the signaling components, and microscopy. Broader Impacts: The broader impact is education of high school biology students on how differential cellular outcomes can be achieved through signal transduction. In collaboration with the UNC outreach program, a teaching module called "Same Genes- Different Fates" will be further developed to teach the concept of differential gene expression and the basis for different cell fates for a set of cells all having the same genes. While the module is currently designed for Biology I and II students (9th and 10th graders), it is adaptable to AP biology and college freshmen. This project will make those adaptations to the higher subject matter by adding concepts like epigenetics and signaling-induced changes into the instructions. The wet-lab part of the module utilizes transgenic plants that have gene promoters driving an enzyme activity that causes different parts of the plant to turn blue. The area of blue is dependent on the type of gene promoter and illustrates differential gene expression. Associated teacher workshops will be held to teach and promote the use of this module. The module will be distributed to high schools initially in North Carolina but eventually nationwide.

智力优势：为了使生物体正常发育并对环境做出适当的反应，组成生物体的细胞必须相互交流。 细胞用来交流的信号可以是激素、光、小分子、电脉冲和触摸。例如，光可以打开（激活）一个光受体，然后激活一些其他的分子复合物，然后激活更多的开关，等等，以提供细胞的变化。在受体的信号和细胞中发生的变化之间是一个称为异源三聚体G蛋白复合物的分子开关。异源三聚体G蛋白偶联信号用于生物体的正常发育以及对引起疾病的病原体的反应。最近的调查异源三聚体G蛋白偶联信号，使用不同的模型系统揭示了一个潜在的范式转变，如何信号激活可以调节。例如，在后生动物和真菌中，活化是限速步骤，并且由配体刺激的细胞表面G蛋白偶联受体（GPCR）催化。 相反，植物调节GTP水解导致静息状态的反向反应，并且在拟南芥中，这种静息状态由跨膜G信号调节因子（RGS）蛋白AtRGS 1维持。 在拟南芥中，D-葡萄糖和/或糖代谢产物是部分由异源三聚体G蛋白复合物介导的信号。 假设葡萄糖和/或糖代谢物通过调节AtRGS 1和AtGPA 1之间的偶联来激活G蛋白途径，并且已经证明D-葡萄糖诱导AtRGS 1而不是AtGPA 1的快速内化。 需要回答的关键问题包括解偶联是如何实现的，解偶联的后果，以及解偶联的分子机制。这些问题将使用数学建模，遗传操作的信号组件，和显微镜检查。 更广泛的影响：更广泛的影响是教育高中生物学生如何通过信号转导实现不同的细胞结果。 与该项目合作，将进一步开发一个名为“相同基因-不同命运”的教学模块，以教授差异基因表达的概念和一组具有相同基因的细胞的不同细胞命运的基础。虽然该模块目前是专为生物I和II学生（9日和10年级），它是适应AP生物和大学新生。 该项目将通过在指令中添加表观遗传学和信号诱导变化等概念来适应更高的主题。该模块的湿实验室部分利用转基因植物，这些植物具有驱动酶活性的基因启动子，该酶活性导致植物的不同部位变蓝。 蓝色区域取决于基因启动子的类型，并说明了差异基因表达。 将举办相关的教师讲习班，以教授和促进使用这一模块。 该模块将分发给高中最初在北卡罗来纳州，但最终在全国范围内。