Signaling mechanisms in plant innate immunity

植物先天免疫的信号机制

基本信息

批准号：
8269029
负责人：
JEN SHEEN
金额：
$ 36.6万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-12 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8269029
关键词：
Agriculture Amino Acids Animals Arabidopsis Autoimmune Diseases BAK1 gene Binding Biochemical Biological Assay Biological Models Case Study Cells Communicable Diseases Complex Defect Detection Environment Evolution Flagellin Future Gene Targeting Genes Genetic Genome Genomics Goals Health Human Immune Immune response Immune system Inflammatory Internet Leucine-Rich Repeat MAP Kinase Gene MAP Kinase Kinase Kinase MAP3K1 gene Mammals Mediating Microbe Mitogen-Activated Protein Kinase Kinases Modeling Molecular Mouse-ear Cress Natural Immunity Pattern Pattern recognition receptor Peptides Phosphorylation Phosphotransferases Plants Play Prevention Production Proteins Receptor Activation Receptor Signaling Regulation Research Research Project Grants Reverse Transcriptase Polymerase Chain Reaction Role Signal Pathway Signal Transduction System Transcriptional Regulation Transgenic Plants Ubiquitination base chromatin immunoprecipitation defense response fly genome wide association study innovation loss of function microbial mutant novel pathogen pattern perception receptor research study tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): Innate Immunity is the most ancient and evolutionarily conserved central defense system that distinguishes host-self from non-self microbial pathogens in plants, animals and humans. It provides the first line of inducible defense against infectious diseases and underlies the prevention of constant and omnipresent microbial invasion. A key function of innate immunity is the detection of microbe-associated molecular patterns (MAMPs, such bacterial flagellin) by pattern recognition receptors and the launch of appropriate defense responses. Recent discoveries have revealed remarkable convergent evolution in the recognition of diverse MAMPs by leucine-rich-repeat receptors and the activation of multiple MAPK cascades in plants, animals and humans. Despite the universal and essential involvement of MAPK cascades in mediating MAMP signaling in plants, worms, flies, mammals and humans, the molecular mechanisms underlying the intertwined signaling webs remain mostly elusive due to the complexity of functional redundancy, mutant lethality and shared components in distinct signaling pathways. The goal of this research project is to establish a regulatory framework for the convergent MAMP signaling using Arabidopsis thaliana as a model system. The proposed experiments aim to integrate molecular, biochemical, cellular, genetic, and genomic approaches to dissect the multifunctional BAK1-MAPKKK complexes and MAPKK-MAPK cascades, and to analyze the downstream WRKY transcription factors in controlling diverse target genes in plant defense responses. Specifically, the project will focus on characterizing and integrating the functions of 15 Arabidopsis genes in flagellin signaling using cell- based assays, transgenic plants and loss-of-function mutants with specific defects in the flagellin receptor FLS2, receptor signaling partner BAK1, MAPKKK-MAPKK-MAPK cascades and WRKY transcription factors. Protein interaction, phosphorylation and ubiquitination assays, quantitative RT- PCR, whole-genome microarray and chromatin-immunoprecipitation will be carried out to elucidate the key and conserved signaling mechanisms in plant innate immunity. Three Specific Aims are: Aim 1. Analyze interactions and regulations of BAK1-MAPKKK signaling complexes Aim 2. Dissect the MAPKK-MAPK cascade functions in convergent MAMP signaling Aim 3. Define functions and regulations of WRKY transcription factors. PUBLIC HEALTH RELEVANCE: The powerful innate immune system underlies the prevention of constant and omnipresent microbial invasion, and provides the first line of inducible defense against infectious diseases in plants, animals and humans. A key function of innate immunity is the detection of microbe- associated molecular patterns (MAMPs) and the launch of appropriate defense responses. Recent discoveries have revealed remarkable convergent evolution in MAMP perception by leucine-rich- repeat pattern recognition receptors and the activation of multiple MAPK cascades. The proposed research from receptor kinase signaling complexes to intertwined MAPK cascades and WRKY transcriptional controls will discover novel and fundamental molecular mechanisms in innate immune signaling, and provide innovative tools for future improvement of agriculture, environment and renewable energy production, as well as human health in treating infectious, inflammatory and autoimmune diseases.

描述（由申请人提供）：先天免疫是最古老且进化上保守的中枢防御系统，可区分植物、动物和人类中的宿主自体与非自体微生物病原体。它提供了针对传染病的第一道诱导性防御，并且是预防持续且无处不在的微生物入侵的基础。先天免疫的一个关键功能是通过模式识别受体检测微生物相关分子模式（MAMP，例如细菌鞭毛蛋白）并启动适当的防御反应。最近的发现揭示了植物、动物和人类中富含亮氨酸重复受体识别不同 MAMP 以及激活多个 MAPK 级联的显着趋同进化。尽管 MAPK 级联普遍且重要地参与介导植物、蠕虫、苍蝇、哺乳动物和人类的 MAMP 信号传导，但由于功能冗余、突变致死性和不同细胞中共享成分的复杂性，相互交织的信号网络背后的分子机制仍然大多难以捉摸。信号通路。该研究项目的目标是以拟南芥为模型系统，建立聚合 MAMP 信号传导的调控框架。所提出的实验旨在整合分子、生化、细胞、遗传和基因组方法来剖析多功能 BAK1-MAPKKK 复合物和 MAPKK-MAPK 级联，并分析控制植物防御反应中不同靶基因的下游 WRKY 转录因子。具体来说，该项目将重点利用基于细胞的测定、转基因植物和在鞭毛蛋白受体FLS2、受体信号传导伙伴BAK1、MAPKKK中具有特定缺陷的功能丧失突变体来表征和整合15个拟南芥基因在鞭毛蛋白信号传导中的功能。 MAPKK-MAPK 级联和 WRKY 转录因子。将通过蛋白质相互作用、磷酸化和泛素化检测、定量RT-PCR、全基因组微阵列和染色质免疫沉淀来阐明植物先天免疫中关键和保守的信号机制。三个具体目标是：目标 1. 分析 BAK1-MAPKKK 信号复合物的相互作用和调节目标 2. 剖析会聚 MAMP 信号传导中的 MAPKK-MAPK 级联功能目标 3. 定义 WRKY 转录因子的功能和调节。公共健康相关性：强大的先天免疫系统是预防持续和无所不在的微生物入侵的基础，并提供了针对植物、动物和人类传染病的第一道诱导性防御。先天免疫的一个关键功能是检测微生物相关分子模式（MAMP）并启动适当的防御反应。最近的发现揭示了富含亮氨酸重复模式识别受体的 MAMP 感知和多个 MAPK 级联激活的显着趋同进化。拟议的从受体激酶信号复合物到相互交织的 MAPK 级联和 WRKY 转录控制的研究将发现先天免疫信号传导中新颖的基本分子机制，并为未来改善农业、环境和可再生能源生产以及人类健康提供创新工具。治疗传染性、炎症和自身免疫性疾病。