Defining the retrograde plastid-to-nucleus stress signaling pathway

定义逆行质体到细胞核应激信号通路

• 批准号: 8729501
• 负责人: KATAYOON DEHESH
• 金额: $ 28.57万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8729501
• 关键词: Acetylation; Address; Animals; Anti-Bacterial Agents; Antibiotics; Antimalarials; Area; Back; Bacteria; Biochemical; Biological; Cell Nucleus; Cells; Cellular Stress; Chemicals; Chloroplasts; Chromatin; Chromatin Structure; Cloning; Code; Communication; Cues; Cyanobacterium; Data; Destinations; Development; Disease; Epigenetic Process; Equilibrium; Eubacterium; Eukaryotic Cell; Genes; Genetic; Genome; Goals; Histone Deacetylase; Histones; Human; Intestines; Investigation; Label; Life; Maps; Mass Spectrum Analysis; Mediating; Metabolic Pathway; Microscopy; Modeling; Modification; Molecular; Monitor; Movement; Mutate; Nuclear Protein; Organelles; Organism; Parasites; Pathway interactions; Perception; Pharmaceutical Preparations; Plants; Plastids; Play; Process; Production; Proteins; Proteome; Proteomics; Reaction; Regulation; Research; Resistance; Role; Route; Signal Pathway; Signal Transduction; Signaling Molecule; Site; Staging; Stress; Transcript; Tubular formation; Validation; Work; analog; base; biological adaptation to stress; combat; gain of function; genome-wide; histone modification; inorganic phosphate; insight; isoprenoid; loss of function; mutant; novel; novel therapeutics; pathogen; pathogenic bacteria; protein complex; protein expression; protein metabolite; protein transport; public health relevance; research study; response; sensor; stoichiometry; tool

DESCRIPTION (provided by applicant): Retrograde signaling is a communication pathway from organelles to nucleus central to regulation and coordination of numerous processes in living organisms, including developmental progressions, responses to biotic and abiotic challenges, protein trafficking and remodeling of chromatin structure. Recently, we have identified the first stress-specific retrograde plastid-to-nucleus signaling metabolite, methylerythritol cyclodiphosphate (MEcPP), an isoprenoid precursor produced by the methylerythritol phosphate (MEP) pathway. This is a conserved signaling pathway that is present in plants, pathogenic bacteria, and in the non- photosynthetic plastids "apicoplast" of the malarial parasite, but is absent in animals. The long-term goal of our research is to gain insight into the regulatory components involved in perception and transduction of the MEcPP signaling cascade that underlies plant responses to stress. Towards this goal, in a collaborative study, we propose to target the following specific objectives: 1: Define cellular components of the MEcPP signaling pathway using genetic and biochemical approaches. 2: Define epigenetic regulators modulated during MEcPP signaling pathway by studying MEcPP regulated class II histone deacetylase (HDAC), and by global mapping of MEcPP-mediated chromatin structural modifications. 3: Determine the role of plastid stromules (stroma filled tubules) in MEcPP-mediated plastid-to-nucleus retrograde signaling using proteomics and cell biological approaches. To undertake these specific objectives we have generated foundational data and unmatched experimental tools including suppressor lines reverted in their ability to induce stress response genes in spite of high MEcPP levels, microarray-based identification of histone deacetylase gene as potential epigenetic regulators of stress responses, and plastid expressing fluorescent protein lines that enable microscopy-based identification of chloroplast tubular extensions called "stromules" found in plants with enhanced MEcPP levels.

描述（由申请人提供）：逆行信号传导是从细胞器到细胞核的通信途径，对生物体中的许多过程的调节和协调至关重要，包括发育进展、对生物和非生物挑战的响应、蛋白质运输和染色质结构的重塑。最近，我们已经确定了第一个应激特异性逆行质体到核的信号代谢产物，甲基环二磷酸（MEcPP），由甲基环二磷酸（MEP）途径产生的类异戊二烯前体。这是一个保守的信号通路，存在于植物、病原细菌和植物的非光合质体“顶质体”中。 疟疾寄生虫，但在动物中不存在。我们的研究的长期目标是深入了解参与感知和转导的MEcPP信号级联反应，植物对压力的反应。为了实现这一目标，在一项合作研究中，我们建议针对以下具体目标：1：使用遗传和生物化学方法定义MEcPP信号通路的细胞组分。第二章：通过研究MEcPP调节的II类组蛋白脱乙酰酶（HDAC）以及MEcPP介导的染色质结构修饰的全球定位来定义MEcPP信号通路中调节的表观遗传调节因子。第三章：使用蛋白质组学和细胞生物学方法确定质体基质（基质填充的小管）在MEcPP介导的质体到核的逆行信号传导中的作用。为了实现这些具体目标，我们已经产生了基础数据和无与伦比的实验工具，包括尽管MEcPP水平高，但抑制系诱导应激反应基因的能力恢复，基于微阵列的组蛋白脱乙酰酶基因作为应激反应的潜在表观遗传调节因子的鉴定，和质体表达荧光蛋白系，其能够基于显微镜鉴定被称为“基质”的叶绿体管状延伸，在MEcPP水平增强的植物中发现。