Genetics of Programmed Cell Death in Arabidoposis

植物，像所有高等真核生物一样，必须控制细胞在发育和发育过程中死亡的发生和蔓延。 对环境信号的反应。植物生物学中充满了发育编程的例子。 细胞死亡(PCD)。植物中PCD的一种特殊形式，称为过敏性反应(HR) 与病原体感染的成功识别和反应相关。人力资源是人力资源的重要组成部分 植物的免疫反应。HR与氧化猝发以及支持和抗死亡的信号有关 向感染部位周围的细胞发出信号。虽然人们对PCD的分子机制知道得很多 在动物中的控制，在植物中知之甚少。 这一建议使用拟南芥作为一个遗传模型，用来理解HR作为一种 植物中PCD的范例。拟南芥基因组已完全测序，几乎没有分子 动物PCD的关键调控因子在序列水平上显著保守的证据。我们是其中之一 第一个认识到利用拟南芥来从遗传上剖析细胞死亡控制的人 对这一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-like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及其相关基因LOL1(LSD One Like 1)和LOL2。LSD1的作用是抑制病毒的传播 正常心率后意外的细胞死亡。质膜NADPH氧化酶衍生的超氧化物 在此过程中与LSD1协同行动。 我们最近证明了LSD1与几种蛋白质相互作用，包括功能相关的 我们证明了bZIP类的一种转录因子(TF)， 在HR和对感染的基础防御中发挥作用。它的活性被LSD1拮抗，它们与 在活体内。我们打算在未来描述其他LSD相互作用的转录因子在细胞死亡和心率中的作用 建议书期间。 我们最近还克隆了第二个抑制失控细胞死亡表型的基因 Isd1突变体。非常令人惊讶的是，这个抑制子编码了一种Nb-LRR类抗病蛋白。 这是第一次发现Nb-LRR类蛋白与病原体以外的其他过程有关 承认。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“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作用是Isd1。这是对这些蛋白质功能的第一次定义， 使我们能够提出他们作为积极的细胞死亡调节者的作用的详细特征。

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.