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Elucidating RIN4_Mediated Immune Signaling Cascades in Arabidopsis

阐明拟南芥中 RIN4_介导的免疫信号级联

基本信息

批准号：
9244034
负责人：
Gitta Laurel Coaker
金额：
$ 31.6万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9244034
关键词：
ATP phosphohydrolase Adaptor Signaling Protein Affect Agriculture Animals Antigen-Antibody Complex Arabidopsis Architecture Binding Biochemical Biological Cells Client Co-Immunoprecipitations Complement Complex Comprehension Coupled Development Disease Disease Resistance Environment Epitopes Eukaryota Event Evolution Flagellin Genetic Genetic Transcription Genotype Hand Health Human Hyperactive behavior Immune Immune response Immune signaling Immune system Immunologic Receptors In Vitro Infection Innate Immune Response Investigation Laboratories Leucine-Rich Repeat Link MAP Kinase Gene Mass Spectrum Analysis Mediating Membrane Modeling Modification Molecular Monitor Mouse-ear Cress Mustard Mutation Natural Immunity Nucleotides Organism Output Perception Phenotype Phosphorylation Plant Proteins Plants Post-Translational Protein Processing Principal Investigator Productivity Protein Family Proteins Pseudomonas Pseudomonas syringae Receptor Activation Receptor Signaling Recombinants Research Resistance Rest Role Signal Transduction Signaling Protein System Tertiary Protein Structure Testing Transgenic Plants Validation Vertebrates Virulence Widespread Disease autoinflammatory disease phenotype disorder control experimental study food security genetic analysis immune activation improved innovation leucine-rich repeat protein member microbial mutant novel pathogen preference programs protein complex public health relevance receptor reconstitution stoichiometry tool ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): The innate, or germline encoded, immune system is an ancient and evolutionary conserved defense system mediating pathogen recognition in humans, animals, and plants. Some innate immune receptors recognize conserved microbial features. Scientific studies have revealed that similar microbial features are recognized across diverse hosts as a result of convergent evolution. For example, in animals, humans and plants bacterial flagellin is recognized by leucine-rich repeat receptors leading to the downstream activation of MAPK cascades and activation of disease resistance. Intracellular immune receptors possessing nucleotide binding, leucine- rich repeat domains (NLRs) act to recognize pathogen effector proteins delivered into plant cells. In humans and animals, NLR receptors can recognize microbial features and, in some cases, effectors. Despite the involvement of analogous immune receptors across diverse organisms, the molecular mechanisms controlling receptor activation and interconnected downstream signaling nodes remain elusive. This is likely due to functional redundancy and lethality underlying key signaling sectors. In this application, we seek to understand the early events underlying NLR receptor activation in plants using the mustard relative, Arabidopsis thaliana, and the bacterial pathogen Pseudomonas syringae as a model. The application will focus on RIN4, a conserved plant protein that can regulate aspects of perception of microbial features, can interact with the NLR receptors RPM1 and RPS2, and is targeted by multiple pathogen effectors. We are able to purify biologically active RPM1 and associated proteins, which will be used to biochemically, investigate NLR receptor activation in vitro. The RPM1 complex will be isolated from Arabidopsis at a resting and activated state and associated proteins will be identified by mass spectrometry. We have optimized conditions for RPM1 complex purification and have several interesting signaling proteins in hand for downstream biochemical, cell biological and genetic validation experiments. The molecular mechanisms controlling effector-induced RIN4 phosphorylation and cleavage for promoting pathogen virulence in susceptible genotypes will be investigated. A greater understanding of how plant immune receptors recognize pathogens will fundamentally advance our understanding of receptor recognition across diverse organisms and is required for the development of novel, environmentally friendly disease control strategies. The specific aims of the project are: 1. Identify changes in complex assembly, enzymatic activity, and known protein associations upon activation of the immune receptor RPM1 in vitro. 2. Identify and characterize NLR protein complexes in a resting and activated state. 3. Investigate the importance of effector-induced RIN4 modifications for interaction with host proteins.

描述（由申请人提供）：先天性或生殖系编码的免疫系统是一种古老的进化保守防御系统，介导人类、动物和植物中的病原体识别。一些先天免疫受体识别保守的微生物特征。科学研究表明，由于趋同进化，不同宿主之间识别出相似的微生物特征。例如，在动物、人类和植物中，细菌鞭毛蛋白被富含亮氨酸的重复受体识别，导致下游MAPK级联的激活和抗病性的激活。具有核苷酸结合的细胞内免疫受体，富含亮氨酸的重复结构域（NLR）用于识别递送到植物细胞中的病原体效应蛋白。在人类和动物中，NLR受体可以识别微生物特征，在某些情况下，还可以识别效应物。尽管在不同的生物体中涉及类似的免疫受体，但控制受体活化和相互连接的下游信号传导节点的分子机制仍然难以捉摸。这可能是由于关键信号部门的功能冗余和致命性。在这个应用程序中，我们试图了解NLR受体激活的早期事件在植物中使用的芥菜相对，拟南芥，和细菌病原体假单胞菌作为一个模型。该申请将集中在RIN 4上，RIN 4是一种保守的植物蛋白，可以调节微生物特征的感知方面，可以与NLR受体RPM1和RPS2相互作用，并被多种病原体效应物靶向。我们能够纯化具有生物活性的RPM 1和相关蛋白，这些蛋白将用于生物化学研究体外NLR受体活化。RPM1复合物将从处于静息和活化状态的拟南芥中分离，相关蛋白将通过质谱法鉴定。我们已经优化了RPM1复合物纯化的条件，并为下游生物化学，细胞生物学和遗传验证实验准备了几种有趣的信号蛋白。将研究控制效应子诱导的RIN 4磷酸化和切割以促进易感基因型中病原体毒力的分子机制。更好地了解植物免疫受体如何识别病原体将从根本上推进我们对不同生物体受体识别的理解，并需要开发新的环境友好的疾病控制策略。该项目的具体目标是：1。确定在体外激活免疫受体RPM1后复合物组装、酶活性和已知蛋白质缔合的变化。2.鉴定和表征处于静息和活化状态的NLR蛋白复合物。3.研究效应子诱导的RIN 4修饰对与宿主蛋白相互作用的重要性。