Genetics of Programmed Cell Death in Arabidoposis

拟南芥程序性细胞死亡的遗传学

• 批准号: 7887640
• 负责人: JEFFERY L. DANGL
• 金额: $ 18.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-17 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7887640
• 关键词: Address; Animals; Apoptosis; Arabidopsis; Biology; Cell Death; Cell membrane; Cells; Cessation of life; Complementary DNA; Development; Disease Resistance; Eukaryota; Family member; Gene Family; Genes; Genetic; Genetic Models; Genetic Programming; Genome; Grant; Immune response; Infection; Informatics; Lead; Length; Molecular; NADPH Oxidase; Oxidative Stress; Pathway interactions; Phenotype; Plant Diseases; Plants; Process; Protein Family; Proteins; Regulation; Research Personnel; Resistance; Respiratory Burst; Rest; Role; Runaway; Salicylic Acids; Series; Signal Transduction; Site; Superoxides; System; Time; Work; Yeasts; Zinc Fingers; base; defense response; in vivo; inhibitor-of-apoptosis protein; interest; leucine-rich repeat protein; loss of function; member; mutant; pathogen; prevent; programs; protein function; reactive oxygen intermediate; response; scaffold; secondary infection; transcription factor; ubiquitin-protein ligase; vpr Genes; yeast two hybrid system

Plants, like all higher eukaryotes, must control the onset and spread of cell death during development and in response to environmental signals. Plant biology is replete with examples of developmentally programmed cell death (PCD). A specialized form of PCD in plants, termed the Hypersensitive Response (HR) is tightly correlated with successful recognition of, and responseto, pathogen infection. The HR is an important part of the plant immune response. HR is associated with an oxidative burst and signaling of pro-and anti-death signals to cells surrounding the infection site. While much is known about the molecular mechanisms of PCD control in animals, very little is known in plants. This proposal uses Arabidopsis as a genetic model with which to understand the control of HR as a paradigm for PCD in plants. The Arabidopsis genome is fully sequenced and there is little molecular evidence for significant conservation of key regulators of animal PCD at the sequence level. We were among the first to recognize the use of Arabidopsis to genetically dissect cell death control and have made significant contributions to the field. We identified and analyzed a series of mutants that mis-regulate HR-like cell death in the absence of pathogen. We cloned three key HR regulators all belonging to one gene family: LSD1 and the related genes LOL1 (LSD One Like 1) and LOL2. LSD1 acts to suppress the spread of unwanted cell death following a normal HR. Superoxide derived from a plasma membrane NADPH oxidase acts in concert with LSD1 in this process. We recently demonstrated that LSD1 interacts with several proteins, including functionally relevant transcription factors (TFs) and putative "metacaspases".We demonstrated that one TF of the bZIP class, functions in HR and in basal defense to infection. Its activity is antagonized by LSD1, and they interact with in vivo. We intend to charaterize the role of the other LSD-interacting TFs in cell death and HR in the coming proposal period. We also recently cloned a second suppressor of the idiosyncratic runaway cell death phenotype of the Isd1 mutant. Very surprisingly, this suppressor encodes a disease resistance protein of the NB-LRR class. This is the first time that an NB-LRR class protein has been implicated in any process other than pathogen recognition. We will investigate how this particular NB-LRR controls the spread of HR-like cell death. We also recently demonstrated that two of the three so-called "metacaspases," identified in Arabidopsis by informatics approaches, and carrying the zinc-finger domain that defines the LSD1 protein family, also function in HR and runaway cell death is Isd1. This is the first definition of a function for these proteins, and allows us to propose a detailed characterization of their action as postive cell death regulators.

植物，像所有高等真核生物一样，必须在发育和发育过程中控制细胞死亡的发生和扩散。 响应环境信号。植物生物学充满了发育程序的例子 细胞死亡（PCD）。植物中 PCD 的一种特殊形式，称为超敏反应 (HR)，与 与成功识别和应对病原体感染相关。人力资源是一个重要的组成部分 植物的免疫反应。 HR 与氧化爆发以及促死亡和抗死亡信号相关 向感染部位周围的细胞发出信号。尽管人们对 PCD 的分子机制了解甚多 对动物的控制，对植物的控制知之甚少。 该提案使用拟南芥作为遗传模型，通过该模型来了解 HR 的控制 植物中 PCD 的范例。拟南芥基因组已完全测序，分子信息很少 动物 PCD 关键调节因子在序列水平上显着保守的证据。我们是其中 第一个认识到利用拟南芥来从基因角度解析细胞死亡控制，并做出了 领域做出了重大贡献。我们鉴定并分析了一系列错误调节 HR 的突变体 在没有病原体的情况下细胞死亡。我们克隆了三个关键的 HR 调节因子，它们都属于一个基因家族： LSD1和相关基因LOL1（LSD One Like 1）和LOL2。 LSD1 的作用是抑制传播 正常 HR 后出现不必要的细胞死亡。源自质膜 NADPH 氧化酶的超氧化物 在此过程中与 LSD1 协同作用。 我们最近证明 LSD1 与多种蛋白质相互作用，包括功能相关的蛋白质 转录因子 (TF) 和推定的“元半胱天冬酶”。我们证明了 bZIP 类的一种 TF， 在 HR 和感染基础防御中发挥作用。它的活性被 LSD1 拮抗，并且它们与 体内。我们打算在未来描述其他 LSD 相互作用的 TF 在细胞死亡和 HR 中的作用 提案期。 我们最近还克隆了特异失控细胞死亡表型的第二个抑制子 Isd1 突变体。非常令人惊讶的是，该抑制蛋白编码 NB-LRR 类抗病蛋白。 这是首次发现 NB-LRR 类蛋白与病原体以外的任何过程有关 认出。我们将研究这种特殊的 NB-LRR 如何控制 HR 样细胞死亡的扩散。 我们最近还证明，在拟南芥中发现的三种所谓的“元天冬酶”中的两种 通过信息学方法，并携带定义 LSD1 蛋白家族的锌指结构域，还 在 HR 和失控细胞死亡中的功能是 Isd1。这是这些蛋白质功能的第一个定义，并且 使我们能够详细描述它们作为细胞死亡积极调节剂的作用。