Glucose Signaling in Plants

描述(申请人提供)：葡萄糖为生命提供燃料，是从大肠杆菌、酵母菌到植物和人类等多种生物生长调节的核心营养信号。尽管葡萄糖在基因表达、生理、代谢、细胞增殖、生长和发育以及人类疾病等方面具有重要的多方面调节作用，但在多细胞动植物中，葡萄糖信号转导的分子和细胞机制仍然是未知的。我们对模式植物拟南芥的研究提供了令人信服的分子、化学和遗传证据，表明己酮酸酶1(HXK1)和雷帕霉素靶标(TOR)激酶是葡萄糖信号中两个进化上保守的主调控因子，它们整合了直接的葡萄糖感应和葡萄糖驱动的能量信号，以协调转录网络和植物对环境信号的响应。我们最近的发现揭示了拟南芥HXK1的两个惊人而独特的功能，它们在没有催化活性的情况下介导葡萄糖信号。在叶片中，HXK1在低硝酸盐的情况下感知过量的葡萄糖，并在细胞核中作用于转录重编程。在硝酸盐充足的条件下，HXK1在直接结合和动员植物激素生长素以促进细胞和器官的大小和生长方面发挥着额外的新功能。我们还开发了新的化学遗传工具，以发现葡萄糖-TOR信号在分生组织激活和胚后植物生长中控制干/祖细胞增殖的一个以前未被认识的核心作用。本研究的目的是阐明拟南芥中葡萄糖感受器HXK1和能量感受器TOR激酶调控葡萄糖信号的分子机制。这些实验旨在将分子、生化、细胞、遗传和基因组学方法结合起来，以全面了解植物生长所必需的葡萄糖信号机制的主要分支，包括HXK1在转录重编程中的非常规作用，HXK1在生长素结合和动员中的新功能，以及葡萄糖-TOR信号调节的转录网络。揭示新的葡萄糖-HXK1和葡萄糖-TOR信号机制的计划将在植物和动物的葡萄糖反应和调控中建立新的范式，并建立一个新的概念框架来增强我们对植物向人类发出葡萄糖信号的分子和细胞机制的理解。目的：1.阐明HXK1作为核糖感受器的调控机制。目的2.研究HXK1在生长素和葡萄糖协同作用中的新功能。目的3.定义一个新的葡萄糖-TOR信号网络，控制细胞周期进入。

DESCRIPTION (provided by applicant): Glucose fuels life and is a central nutrient signal for growth regulation in a broad range of organisms from E. coli, yeasts to plants and humans. Despite the essential and multifaceted regulatory roles of glucose in gene expression, physiology, metabolism, cell proliferation, growth and development, and human diseases, the molecular and cellular mechanisms of glucose signaling remain elusive in multicellular plants and animals. Our research in the model plant Arabidopsis thaliana has provided compelling molecular, chemical and genetic evidence that hexokinase1 (HXK1) and target-of-rapamycin (TOR) kinase are two evolutionarily conserved master regulators in glucose signaling, which integrate direct glucose sensing and glucose-driven energy signaling to orchestrate transcriptional networks and plant growth in response to environmental cues. Our recent findings uncover two surprising and distinct functions of Arabidopsis HXK1 that mediate glucose signaling without its catalytic activity. In leaves, HXK1 senses excess glucose at low nitrate and acts in the nucleus to modulate transcriptional reprogramming. In nitrate sufficient conditions, HXK1 plays an additional novel function in direct binding and mobilization of the phytohormone auxin to promote cell and organ size and growth. We have also developed new chemical genetic tools to discover a previously unrecognized central role of glucose-TOR signaling in controlling stem/progenitor cell proliferation in meristem activation and postembryonic plant growth. The goal of this research project is to elucidate the molecular mechanisms of glucose signaling controlled by the glucose sensor HXK1 and the energy sensor TOR kinase in Arabidopsis. The proposed experiments are designed to integrate molecular, biochemical, cellular, genetic, and genomic approaches to reach a comprehensive understanding on major branches of glucose signaling mechanisms central to plant growth, including the unconventional role of HXK1 in transcriptional reprogramming, the novel function of HXK1 in auxin binding and mobilization, as well as the transcriptional network modulated by glucose-TOR signaling. The project on uncovering the novel glucose-HXK1 and glucose-TOR signaling mechanisms will establish new paradigms in glucose responses and regulations in plants and animals, and 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 regulatory mechanism of HXK1 functions as a nuclear glucose sensor. Aim 2. Characterize the novel HXK1 functions in auxin and glucose synergism. Aim 3. Define the novel glucose-TOR signaling network gating the cell cycle entry.