Molecular Basis of Pathogen-Induced Cell Death in Plants

病原体诱导植物细胞死亡的分子基础

• 批准号: 7194497
• 负责人: Jean T. Greenberg
• 金额: $ 34.54万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194497
• 关键词: Arabidopsis; ankyrins; apoptosis; biological signal transduction; cell type; chlorophyll; chloroplasts; gene expression; immunoelectron microscopy; light microscopy; membrane proteins; mitochondria; molecular cloning; molecular genetics; molecular pathology; pathologic process; plant diseases; plant genetics; plant growth regulators; protein protein interaction; regulatory gene; single cell analysis; video microscopy; yeast two hybrid system

DESCRIPTION (provided by applicant): Experiments in this competing renewal combine the powerful genetic tools of the model plant Arabidopsis with cell biological and biochemical approaches to examine a major signaling pathway that controls innate immunity and programmed cell death (PCD). The control of plant defenses has many parallels with human innate immunity. Furthermore, PCD has similar features and regulation in plants and humans. Our long term goal is to understand the molecular basis of PCD regulation and execution. This is essential for developing strategies to manipulate PCD to prevent or cure diseases involving excess or insufficient PCD induction in both plants and humans. What is learned from studying plant immunity and PCD will be a paradigm for understanding similar events in humans. Experiments described herein build on previous work on two Arabidopsis genes, ACD6 and ACD2. ACD6 is a novel integral plasma membrane protein with an N- terminal ankyrin repeat domain that controls defense and PCD in plants. Ankyrin repeats are involved in protein-protein interactions in plants, humans and many other organisms. ACD6 is important for both local and systemic signaling during infection. ACD2 is a novel protein that controls the activation and extent of PCD during infection by controlling the levels or reactivity of an endogenous PCD-inducing molecule that is either a porphyrin or a porphyrin-like molecule. Thus, infection activates ACD6 to regulate defenses and PCD and ACD2 modulates the timing and extent of PCD to prevent excess tissue damage. The proposed research aims to: (i) determine the mechanism of action of ACD6 in activating PCD and disease resistance using molecular genetic and biochemical approaches; (2) determine the mechanism of action of ACD2 by combining molecular genetic, biochemical and physiological experiments; and (3) discern the properties and signaling requirements of cells that die due to porphyrin treatment (a surrogate for infection) using cell biological approaches. Porphyrins are important in anti-tumor therapies being developed. Therefore, it is important to know as much as possible about the effects that porphyrins have on cells. Dis-regulation of porphyrins in human (a condition called porphyria) causes severe disease to humans. ACD2 may provide a way to help people with this disease, since it likely has the potential to detoxify porphyrins. A number of human diseases are also caused by the malfunction of ankyrin-containing proteins. This work will generate important information about the whole class of ankyrin proteins that can be applied to understanding and possibly interrupting some human diseases. These studies will unravel common processes in plants and humans that can be manipulated to treat diseases caused by too much or too little cell damage. Because experimental progress using a plant model is rapid, the results obtained and quickly be related to human biology and disease.

描述（由申请人提供）：这种竞争性更新的实验将模式植物拟南芥的强大遗传工具与细胞生物学和生物化学方法相结合，以检查控制先天免疫和程序性细胞死亡（PCD）的主要信号通路。植物防御的控制与人类先天免疫有许多相似之处。此外，PCD在植物和人类中具有相似的特征和调节。我们的长期目标是了解PCD调节和执行的分子基础。这对于开发策略来操纵PCD以预防或治疗植物和人类中涉及PCD诱导过量或不足的疾病是至关重要的。从研究植物免疫和PCD中学到的东西将成为理解人类类似事件的范例。本文描述的实验建立在先前对两个拟南芥基因ACD 6和ACD 2的工作上。ACD 6是一种新的整合质膜蛋白，其N端具有锚蛋白重复结构域，控制植物的防御和PCD。锚蛋白重复序列参与植物、人类和许多其他生物体中的蛋白质-蛋白质相互作用。ACD 6对于感染期间的局部和全身信号传导都很重要。ACD 2是一种新的蛋白质，其通过控制内源PCD诱导分子的水平或反应性来控制感染期间PCD的活化和程度，所述内源PCD诱导分子是卟啉或卟啉样分子。因此，感染激活ACD 6以调节防御和PCD，并且ACD 2调节PCD的时间和程度以防止过度的组织损伤。拟议的研究旨在：（i）使用分子遗传学和生物化学方法确定ACD 6在激活PCD和疾病抗性中的作用机制;（2）通过结合分子遗传学、生物化学和生理学实验确定ACD 2的作用机制;和（3）使用细胞生物学方法辨别由于卟啉处理（感染的替代物）而死亡的细胞的性质和信号传导要求。 卟啉在正在开发的抗肿瘤疗法中是重要的。因此，尽可能多地了解卟啉对细胞的影响是很重要的。人类卟啉的失调（一种称为卟啉症的疾病）会导致严重的疾病。ACD 2可能提供一种帮助患有这种疾病的人的方法，因为它可能具有解毒卟啉的潜力。许多人类疾病也是由含锚蛋白的功能障碍引起的。这项工作将产生关于整类锚蛋白的重要信息，这些信息可用于理解和可能中断某些人类疾病。这些研究将揭示植物和人类的共同过程，这些过程可以被操纵来治疗由细胞损伤过多或过少引起的疾病。由于使用植物模型的实验进展迅速，所获得的结果很快与人类生物学和疾病有关。