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.

免疫信号感知和细胞表面受体和肽配体的整合 植物和动物依靠模式识别受体（PRR）来通过识别微生物来检测感染 相关的分子模式（MAMP）。植物质膜（PM） - 居民受体激酶（RKS）功能 随着prrs感知到来自不同微生物的肿胀并共同有助于植物免疫。植物rks也是 感知广泛的外在和内在信号，并调节生长，繁殖和环境 适应。许多RKS介导的信号通路在RKS的亚家族中收敛，即 bak1/serks，该功能充当共享的共素，在配体感知时与各种受体相关联 调节植物免疫，生长和免疫稳态。 PM螺旋细胞质激酶Bik1 与多个PRR-BAK1复合物相关联，并传递细胞内信号事件。微生物感染 还诱导许多分泌的肽的基因表达，它们可以用作免疫调节 PRRS感知并加强植物免疫力所感知的植物细胞因子。该提议的长期目标是阐明 PRR复合物通过共享模块中的病原体信号感知和整合的机制 与植物细胞因子的协调，以快速，特异性和健壮的免疫反应。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 动力学是通过时空调节的，并传递了多样的免疫信号传导。作为关键激酶，Bik1 稳态，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 CORECEPTORS如何维护 不同受体中的功能特异性。研究将解决如何调节信号特异性 具有在生物水平的单细胞分辨率。该项目还将研究免疫调节 植物细胞因子与微生物模式协调以实现有效免疫。拟议的跨学科 研究将为不同级别的研究人员提供足够的培训机会，包括代表性不足 本科生和研究生以及博士后研究员，并将促进我们对先天的理解 通过识别新成分并描绘出来，在整个生物水平上的免疫力和信号转导 调节免疫信号整合，信号激活，衰减和特异性的新途径。