GENETICS OF PROGRAMMED CELL DEATH IN ARABIDOPSIS

描述：该提案旨在分子和遗传 理解决定时间和控制的过程 在容易操作的高等植物模型中的程序性细胞死亡， 拟南芥 结果将是至关重要的建设 高等真核生物细胞死亡控制的一般模型。 这些 实验将开始，以澄清细胞死亡的控制， 植物抗病反应和正常发育。 结果 这些实验可以与新兴的细胞死亡模型进行对比， 其他生物的调节，以询问分子机制是否 相关的，或者很大程度上是不同的。 具体目标取决于前 表现出异常细胞死亡拟南芥突变体的鉴定 控制 这些突变定义了四个位点（称为lsd 1和lsd 3-lsd 5 基于其病变模拟疾病抗性表型），以及许多 新的变种人已经出现了 LSD突变体类可以分为 控制细胞死亡起始的基因座和决定 细胞死亡的传播一旦开始。 这些突变体 表现出细胞类型特异性的细胞死亡的发病暗示空间 发展控制。 我们最近分离出了LSD 1基因， 定义了限制传播所涉及的基因座的传播类 细胞死亡，并表明它编码一种新的锌指亚类， 蛋白 我们最近还证明了野生型LSD 1具有双重表达。 功能，两者都响应于超氧化物依赖性信号。 的 第一个功能是通过细胞死亡抑制组成性通量 途径，第二是防止细胞死亡的猖獗传播 一旦启动。 这一提议与控制细胞死亡 如LSD 1所定义的增殖，伴随着细胞死亡的开始， 以LSD 5为例。 我们提出四个具体目标：第一， 在细胞生物学水平上了解LSD 1如何发挥其功能。 目的二是对LSD 1信号转导通路进行基因解剖， 通过分离LSD 1表型的基因外抑制子。 这些 将被放置到互补组，映射，并测试他们的 抑制由外部触发引起的细胞死亡的能力，例如 病原体，以及“起始类”突变。 目标三是完成 目的四是对lsd 5基因进行详细的分析， LSD 5的基因外抑制因子，这将与LSD 1的研究平行 抑制剂

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.