Glucose Signaling in Plants

植物中的葡萄糖信号传导

• 批准号: 8244479
• 负责人: JEN SHEEN
• 金额: $ 36.43万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2014-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8244479
• 关键词: ATP phosphohydrolase; Age; Agriculture; Animal Model; Animals; Arabidopsis; Binding; Biochemical; Cell Death; Cell Nucleus; Cell Proliferation; Cells; Chromatin; Complex; Cues; DNA Binding; Defect; Development; Diabetes Mellitus; Diffuse; Environment; Enzymes; Escherichia coli; Eukaryota; Future; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Transcription; Genome; Genomics; Glucose; Goals; Growth; Growth and Development function; Health; Hormones; Human; Malignant Neoplasms; Mediating; Metabolic; Metabolism; Modeling; Molecular; Molecular Conformation; Mouse-ear Cress; Nuclear; Nutrient; Obesity; Oranges; Organ; Organism; PAX3 gene; PAX7 gene; Pattern; Physiology; Plant Model; Plant Roots; Plants; Play; Production; Proteomics; Regulation; Repression; Research; Research Project Grants; Role; Scaffolding Protein; Seedling; Signal Transduction; Signaling Molecule; Transgenic Plants; Yeasts; base; cell type; chromatin immunoprecipitation; genome wide association study; glucose metabolism; glucose sensor; human disease; in vivo; innovation; insulin signaling; loss of function; mutant; novel; plant growth/development; research study; response; sensor; tool; transcription factor

DESCRIPTION (provided by applicant): Glucose is an ancient and central signaling molecule in a broad range of organisms from E. coli, yeast to plants and humans. Despite the essential roles of glucose in gene expression, physiology, metabolism, cell proliferation and death, growth and development, and human diseases, the molecular and cellular mechanisms of glucose signaling remain mostly elusive in plants and animals. Our research in the model plant Arabidopsis thaliana has provided compelling genetic and biochemical evidence that hexokinase1 (HXK1) is an evolutionarily conserved glucose sensor that integrates nutrient and hormone signals to govern gene expression and plant growth in response to environmental cues. How the metabolic enzyme mediates glucose signaling remains a mystery. Our recent findings indicate that Arabidopsis HXK1 mediates glucose signaling without its metabolic activity, and interacts with two HXK1 Unconventional Partners (HUP1: a scaffolding protein interacting with HXK1, HUP2 and transcription factors (TFs); HUP2: an ATPase interacting with HXK1, HUP1 and other ATPases) in the nucleus to control transcription and diverse glucose responses. The goal of this research project is to elucidate the mechanisms of glucose signaling controlled by the nuclear sensor HXK1 in Arabidopsis. The proposed experiments aim to use molecular, cellular, genetic, and genomic approaches to elucidate HXK1 functions and regulation, and to analyze two sets of signaling regulators acting downstream of the nuclear HXK1-HUP1/2 complex. The project will focus on characterizing and integrating functions of eight Arabidopsis genes in glucose signaling using transgenic plants and loss-of-function mutants with specific defects in the glucose sensor HXK1, HXK1 signaling partners HUP1, novel transcription factors (MYB, SCL3, ZFP) and ATPases (HUP2/RPT5, RPT2 and RPT6). Near whole-genome microarray and chromatin-immunoprecipitation (ChIP) will be carried out to identify the primary HXK1 target genes and characterize their regulation in vivo. The project challenges the existing paradigm on metabolism-based glucose responses in plants and animals, and aims to build a new conceptual framework to enhance our understanding of the molecular and cellular mechanisms of glucose signaling from plants to humans. Three Specific Aims are: Aim 1. Elucidate the functions and regulation of the nuclear glucose sensor HXK1 Aim 2. Characterize three novel TFs in HXK1-HUP1/2-mediated glucose signaling Aim 3. Define functions of three ATPases in the nuclear RPT5/2/6 complex. PUBLIC HEALTH RELEVANCE: In spite the central roles of glucose in gene expression, physiology, metabolism, cell proliferation and death, growth and development, and human diseases, the molecular mechanisms of glucose signaling remain elusive in plants and animals. Our recent research has provided compelling evidence that glucose signaling can be uncoupled from glucose metabolism in multicellular eukaryotes, and Arabidopsis hexokinase1 acts as an evolutionarily conserved sensor playing a pivotal role in nuclear glucose signaling. The proposed research will discover novel regulators and elucidate their functions in nuclear glucose signaling, and provide innovative tools for future improvement of agriculture, environment and renewable energy production, as well as human health in treating diabetes, obesity, cancer and ageing modulated by glucose signaling.

描述（由申请人提供）：葡萄糖是一种古老且重要的信号分子，存在于从大肠杆菌、酵母到植物和人类的多种生物体中。尽管葡萄糖在基因表达、生理学、代谢、细胞增殖和死亡、生长和发育以及人类疾病中发挥着重要作用，但植物和动物中葡萄糖信号传导的分子和细胞机制仍然大多难以捉摸。我们对模式植物拟南芥的研究提供了令人信服的遗传和生化证据，证明己糖激酶1 (HXK1) 是一种进化上保守的葡萄糖传感器，它整合营养和激素信号来控制基因表达和植物生长以响应环境线索。代谢酶如何介导葡萄糖信号仍然是个谜。我们最近的研究结果表明，拟南芥 HXK1 在没有代谢活性的情况下介导葡萄糖信号传导，并与两个 HXK1 非常规伙伴相互作用（HUP1：与 HXK1、HUP2 和转录因子 (TF) 相互作用的支架蛋白；HUP2：与 HXK1、HUP1 和转录因子 (TF) 相互作用的 ATP 酶）其他 ATP 酶）在细胞核中控制转录和不同的葡萄糖反应。该研究项目的目标是阐明拟南芥中核传感器 HXK1 控制的葡萄糖信号传导机制。拟议的实验旨在使用分子、细胞、遗传和基因组方法来阐明 HXK1 功能和调节，并分析作用于核 HXK1-HUP1/2 复合物下游的两组信号调节因子。该项目将重点利用转基因植物和在葡萄糖传感器 HXK1、HXK1 信号伙伴 HUP1、新型转录因子（MYB、SCL3、ZFP）中具有特定缺陷的功能丧失突变体来表征和整合八个拟南芥基因在葡萄糖信号传导中的功能和 ATP 酶（HUP2/RPT5、RPT2 和 RPT6）。将进行近全基因组微阵列和染色质免疫沉淀 (ChIP)，以确定主要的 HXK1 靶基因并表征其体内调控。该项目挑战了植物和动物中基于代谢的葡萄糖反应的现有范式，旨在建立一个新的概念框架，以增强我们对从植物到人类的葡萄糖信号传导的分子和细胞机制的理解。三个具体目标是： 目标 1. 阐明核葡萄糖传感器 HXK1 的功能和调节 目标 2. 表征 HXK1-HUP1/2 介导的葡萄糖信号传导中的三种新型 TF 目标 3. 定义核 RPT5/2 中三种 ATP 酶的功能/6 复合体。公共健康相关性：尽管葡萄糖在基因表达、生理学、代谢、细胞增殖和死亡、生长和发育以及人类疾病中发挥着核心作用，但植物和动物中葡萄糖信号传导的分子机制仍然难以捉摸。我们最近的研究提供了令人信服的证据，证明多细胞真核生物中葡萄糖信号传导可以与葡萄糖代谢脱钩，而拟南芥己糖激酶1作为一种进化上保守的传感器，在核葡萄糖信号传导中发挥着关键作用。拟议的研究将发现新型调节剂并阐明其在核葡萄糖信号传导中的功能，并为未来改善农业、环境和可再生能源生产以及通过葡萄糖信号传导调节的糖尿病、肥胖、癌症和衰老的治疗以及人类健康提供创新工具。