GENETICS OF PROGRAMMED CELL DEATH IN ARABIDOPSIS

描述：这项提议针对的是一种分子和基因 了解决定时间安排和控制的流程 容易操纵的高等植物模型中的程序性细胞死亡， 拟南芥。结果将是建设的关键 高等真核生物细胞死亡控制的概括性模型。这些 实验将开始阐明在这两种情况下细胞死亡的控制 植物抗病反应和正常发育。结果来自 这些实验可以与新兴的细胞死亡模型进行对比。 在其他生物体中的调节，以询问分子机制是否 相关的，或大体不同的。具体目标取决于前一个目标 拟南芥细胞异常死亡突变体的鉴定 控制力。这些突变定义了四个基因座(称为Lsd1和lsd3-lsd5 基于它们的病变模拟抗病表型)，以及许多 新的突变体现已问世。LSD突变体类别可以分为 控制细胞死亡的基因座和决定细胞死亡的基因座 一旦细胞死亡开始，细胞死亡的繁殖。这些变种人 细胞死亡的开始表现出细胞类型的特异性，暗示着空间 和发育控制。我们最近分离了LSD1基因，它 定义限制传播所涉及的位置的传播类 发现它编码了一个新的锌指亚类 蛋白。我们最近还证明了野生型LSD1具有双重 功能，两者都对超氧化物依赖的信号做出反应。这个 第一个功能是通过细胞死亡来抑制本构通量 途径，第二是防止细胞死亡的猖獗繁殖 一旦它被启动。这项提议与控制细胞死亡形成对比。 如LSD1所定义的，随着细胞死亡的开始， 以lsd5为例。我们提出了四个具体目标：一是 在细胞生物学水平上了解LSD1是如何执行其功能的。 目的二是对LSD1信号转导通路进行遗传学解剖， 通过分离LSD1表型的基因外抑制物。这些 将被放入互补组，绘制地图，并进行测试 抑制由外部触发因素引起的细胞死亡的能力，例如 病原体，并由“启蒙类”突变。目标三是完成 克隆了lsd5基因，目的四是详细分析 LSD5的外源抑制因子将与LSD1的研究平行 压迫者。

DESCRIPTION: This proposal aims at a molecular and genetic understanding of processes determining the timing and control of programmed cell death in the easily manipulated model higher plant, Arabidopsis thaliana. Results will be critical in building generalizable models of cell death control in higher eukaryotes. These experiments will begin to clarify the control of cell death during both plant disease resistance responses and normal development. Results from these experiments can be contrasted to emerging models of cell death regulation in other organisms to ask whether molecular mechanisms are related, or largely divergent. The specific aims rest on the previous identification of Arabidopsis mutants which exhibit aberrant cell death control. These mutations defined four loci (termed lsd1 and lsd3-lsd5 based on their Lesion Simulating Disease Resistance phenotype), and many new mutants are now available. The lsd mutant class can be divided into loci controlling the initiation of cell death and loci which determine the propagation of cell death once it is initiated. These mutants exhibit cell-type specificity for onset of cell death implying spatial and developmental control. We recently isolated the LSD1 gene, which defines the propagation class of loci involved in limiting the spread of cell death, and showed that it encodes a novel zinc finger subclass protein. We also recently demonstrated that wild type LSD1 has a dual function, both of which respond to a superoxide-dependent signal. The first function is to dampen constitutive flux through a cell death pathway, and the second is to prevent rampant propagation of cell death once it is initiated. This proposal contrasts the control of cell death propagation, as defined by lsd1, with the initiation of cell death, exemplified by lsd5. We propose four Specific Aims: The first is to understand at a cell biology level how LSD1 carries out its functions. Aim two is genetic dissection of the LSD1 signal transduction pathway, via isolation of extragenic suppressors of the lsd1 phenotype. These will be placed into complementation groups, mapped, and tested for their ability to suppress cell death caused by external triggers, such as pathogens, and by "initiation class" mutations. Aim three is to finish cloning of the lsd5 gene, and aim four is a detailed analysis of extragenic suppressors of lsd5 which will parallel the study of lsd1 supressors.