Glucose Signaling in Plants

描述（由申请人提供）：葡萄糖是生命的燃料，是一种重要的营养信号，用于从大肠杆菌到多种生物的生长调节。大肠杆菌、酵母菌到植物和人类。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中具有重要的多方面调节作用，但葡萄糖信号传导的分子和细胞机制在多细胞植物和动物中仍然是难以捉摸的。我们在模式植物拟南芥中的研究提供了令人信服的分子、化学和遗传证据，证明己糖激酶1（HXK 1）和雷帕霉素靶蛋白（TOR）激酶是葡萄糖信号传导中两个进化上保守的主调节因子，它们整合了直接葡萄糖传感和葡萄糖驱动的能量信号传导，以协调转录网络和植物生长对环境信号的响应。我们最近的发现揭示了拟南芥HXK 1的两个令人惊讶的和不同的功能，介导葡萄糖信号而没有其催化活性。在叶子中，HXK 1在低硝酸盐时感知过量的葡萄糖，并在细胞核中起作用以调节转录重编程。在硝酸盐充足的条件下，HXK 1在直接结合和动员植物激素生长素以促进细胞和器官大小和生长方面发挥额外的新功能。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/祖细胞增殖的先前未被认识的中心作用。本研究旨在阐明拟南芥中葡萄糖传感器HXK 1和能量传感器TOR激酶调控葡萄糖信号的分子机制。这些实验旨在整合分子、生物化学、细胞、遗传学和基因组学方法，以全面了解对植物生长至关重要的葡萄糖信号传导机制的主要分支，包括HXK 1在转录重编程中的非常规作用，HXK 1在生长素结合和动员中的新功能，以及葡萄糖-TOR信号传导调节的转录网络。该项目将为植物和动物的葡萄糖反应和调控建立新的范式，并建立一个新的概念框架，以增强我们对葡萄糖信号从植物到人类的分子和细胞机制的理解。三个具体目标是：目标1。阐明HXK 1作为核葡萄糖传感器功能的调节机制。目标2.表征HXK 1在生长素和葡萄糖协同作用中的新功能。目标3.定义新的葡萄糖-TOR信号网络门控细胞周期进入。

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.