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化的例子， 细胞死亡（PCD）。植物中PCD的一种特殊形式，称为过敏反应（HR）， 与成功识别和应答病原体感染相关。人力资源是一个重要的组成部分， 植物的免疫反应HR与氧化爆发和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。虽然对PCD的分子机制了解很多， 在动物中的控制，在植物中知之甚少。 该建议使用拟南芥作为遗传模型，以了解HR的控制作为一种遗传模型。 植物中PCD的范例。拟南芥基因组已完全测序， 在序列水平上动物PCD的关键调控因子的显著保守性的证据。我们在 第一个认识到利用拟南芥基因解剖细胞死亡控制， 对外地的重大贡献。我们鉴定并分析了一系列错误调节HR样的突变体， 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调节子，它们都属于一个基因家族： LSD 1和相关基因LOL 1（LSD One Like 1）和LOL 2。LSD 1的作用是抑制 正常HR后不必要的细胞死亡。来自质膜NADPH氧化酶的超氧化物 在这个过程中与LSD 1协同作用。 我们最近证明LSD 1与几种蛋白质相互作用，包括功能相关的蛋白质， 转录因子（TF）和推定的“后半胱氨酸天冬氨酸蛋白酶”。我们证明了bZIP类的一种TF， 在HR和对感染的基础防御中起作用。其活性被LSD 1拮抗，并且它们与 in vivo.我们打算在未来的研究中进一步阐明其他LSD相互作用的TF在细胞死亡和HR中的作用。 建议期。 我们最近还克隆了第二个特异质失控细胞死亡表型的抑制基因， Isd 1突变体。非常令人惊讶的是，该抑制基因编码NB-LRR类的抗病蛋白。 这是第一次NB-LRR类蛋白质与病原体以外的任何过程有关 识别.我们将研究这种特殊的NB-LRR如何控制HR样细胞死亡的传播。 我们最近还证明了在拟南芥中发现的三种所谓的“后半胱氨酸蛋白酶”中的两种， 通过信息学方法，并携带定义LSD 1蛋白家族的锌指结构域，还 在HR和失控细胞死亡中起作用的是Isd 1。这是这些蛋白质功能的第一个定义， 使我们能够提出一个详细的表征他们的行动作为积极的细胞死亡调节剂。