Immune signal perception and integration by cell surface receptors and peptide liga

细胞表面受体和肽连接体的免疫信号感知和整合

• 批准号: 10890399
• 负责人: Libo Shan
• 金额: $ 39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10890399
• 关键词: Animals; BAK1 gene; Cell Surface Receptors; Cell membrane; Cell surface; Cells; Complex; Cytoplasm; Eukaryota; Event; Feedback; Gene Expression; Goals; Growth; Homeostasis; Immune; Immune response; Immune signaling; Immunity; Infection; Interdisciplinary Study; Ligands; Mediating; Microbe; Modification; Molecular; Natural Immunity; Pathway interactions; Pattern; Pattern recognition receptor; Peptides; Perception; Phosphorylation; Phosphotransferases; Plants; Post-Translational Protein Processing; Postdoctoral Fellow; Process; Receptor Signaling; Reproduction; Research; Research Personnel; Resolution; Signal Pathway; Signal Transduction; Specificity; Ubiquitination; attenuation; environmental adaptation; fortification; graduate student; immunoregulation; microbial; novel; pathogen; receptor; spatiotemporal; training opportunity; undergraduate student

Immune signal perception and integration by cell surface receptors and peptide ligands Plants and animals rely on pattern-recognition receptors (PRRs) to detect infection by recognizing microbe- associated molecular patterns (MAMPs). Plant plasma membrane (PM)-resident receptor kinases (RKs) function as PRRs that sense MAMPs from diverse microbes and collectively contribute to plant immunity. Plant RKs also perceive a wide range of extrinsic and intrinsic signals and regulate growth, reproduction, and environmental adaptation. The signaling pathways mediated by many RKs converge at a subfamily of RKs, namely BAK1/SERKs, that function as shared coreceptors associating with various receptors upon ligand perception modulating plant immunity, growth, and immune homeostasis. The PM-tethered cytoplasmic kinase BIK1 associates with multiple PRR-BAK1 complexes and relays the intracellular signaling events. Microbial infection also induces the gene expression of many secreted peptides, which could function as immunomodulatory phytocytokines perceived by PRRs and fortify plant immunity. This proposal's long-term goal is to elucidate the mechanisms underlying pathogen signal perception and integration by PRR complexes via shared modules in coordination with phytocytokines for a rapid, specific, and robust immune response. The proposed research will address several key questions in the field. The project will elucidate how BIK1-associated PRR receptorsome dynamics are spatiotemporally regulated and relay the diverse immune signaling. As a critical kinase, BIK1 homeostasis, activities, and subcellular dynamics are regulated by the intertwined phosphorylation and ubiquitination modifications. The project will define how the shared BAK1/SERK coreceptors maintain the functional specificity in different receptorsomes. The studies will address how signaling specificity is regulated with the single-cell resolution at the organismal level. The project will also study how immunomodulatory phytocytokines coordinate with microbial patterns to mount effective immunity. The proposed interdisciplinary research will provide ample training opportunities for researchers at different levels, including underrepresented undergraduate and graduate students and postdoctoral fellows, and will advance our understanding of innate immunity and signal transduction at the whole organismal level by identifying new components and delineating novel pathways that regulate immune signal integration, signaling activation, attenuation, and specificity.

细胞表面受体和肽配体的免疫信号感知和整合 植物和动物依靠模式识别受体（PRR）通过识别微生物来检测感染。 相关分子模式（MAMP）。植物质膜 (PM) 驻留受体激酶 (RK) 功能 PRR 可以感知来自不同微生物的 MAMP，并共同促进植物免疫。植物 RK 还 感知广泛的外在和内在信号并调节生长、繁殖和环境 适应。由许多 RK 介导的信号通路汇聚于 RK 的一个亚家族，即 BAK1/SERK，作为共享辅助受体在配体感知时与各种受体相关联 调节植物免疫力、生长和免疫稳态。 PM 束缚的细胞质激酶 BIK1 与多个 PRR-BAK1 复合物结合并传递细胞内信号事件。微生物感染 还诱导许多分泌肽的基因表达，这些肽可以起到免疫调节作用 PRR 感知植物细胞因子并增强植物免疫力。该提案的长期目标是阐明 PRR 复合物通过共享模块识别和整合病原体信号的机制 与植物细胞因子协调，产生快速、特异性和强大的免疫反应。拟议的研究将 解决该领域的几个关键问题。该项目将阐明 BIK1 相关的 PRR 受体如何 动力学受到时空调节并传递不同的免疫信号。作为一种关键激酶，BIK1 体内平衡、活动和亚细胞动力学受到相互交织的磷酸化和 泛素化修饰。该项目将定义共享的 BAK1/SERK 核心受体如何维持 不同受体体的功能特异性。这些研究将解决如何调节信号特异性 具有生物体水平的单细胞分辨率。该项目还将研究免疫调节剂如何 植物细胞因子与微生物模式协调以提高有效的免疫力。拟议的跨学科 研究将为不同级别的研究人员提供充足的培训机会，包括代表性不足的研究人员 本科生、研究生和博士后研究员，并将增进我们对先天的理解 通过识别新成分并描绘整个有机体水平的免疫和信号转导 调节免疫信号整合、信号激活、减弱和特异性的新途径。