Function and regulation of two key serine proteases in insect immunity

两种关键丝氨酸蛋白酶在昆虫免疫中的功能和调控

• 批准号: 10246410
• 负责人: HAOBO JIANG
• 金额: $ 34.55万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246410
• 关键词: Antibodies; Area; Bacteria; Binding Proteins; Biochemical; Biological Assay; Chemicals; Clip; Collection; Complex; Constitution; Culicidae; Data; Defense Mechanisms; Detection; Disease Vectors; Drosophila genus; Enzyme Precursors; Evolution; Fractionation; Future; Genes; Genetic; Genome; Glucans; Goals; Gram-Negative Bacteria; Gram-Positive Bacteria; Hemolymph; Histidine; Immune; Immune response; Immune signaling; Immunity; Infection; Innate Immune System; Insect Vectors; Insecta; Invaded; Investigation; Knowledge; Larva; Lead; Ligands; Malaria; Manduca; Manduca sexta; Mass Spectrum Analysis; Mediating; Melanins; Microbe; Modeling; Molecular; Molecular Probes; Monophenol Monooxygenase; Natural Immunity; Organism; Orthologous Gene; Parasites; Pathway interactions; Peptide Hydrolases; Peptides; Peptidoglycan; Plasma; Play; Process; Production; Property; Protein Biosynthesis; Proteins; Recombinant Proteins; Regulation; Research; Role; Serine Protease; Signal Pathway; Signal Transduction; Specificity; Stress; Study models; System; Testing; antimicrobial; antimicrobial peptide; base; biochemical model; cytokine; defense response; experience; extracellular; fungus; human disease; improved; innate immune pathways; insect disease vector; insight; pathogen; peptidoglycan recognition protein; public health relevance; response; thioester; transmission process; vector

Project Summary Extracellular serine proteases and their non-catalytic homologs coordinate key defense mechanisms in insects. This includes responses of mosquitoes against pathogens and parasites that cause serious human diseases. Proteolytic cleavage generates active phenoloxidases (POs), thioester proteins (TEPs), Spätzle and other cytokines. PO catalyzes the production of reactive chemicals to sequester and kill the invading organisms. TEPs opsonize parasites, targeting them for destruction. Spätzle and other cytokines trigger intracellular signaling pathways to induce the expression of antimicrobial peptides and other defense proteins. In insect vectors of human diseases, the protease networks may be evaded or disrupted by proteins from the intruders. Knowledge of the system components and their interactions from biochemical model insects such as Manduca sexta is useful for gaining detailed molecular understanding of fundamental aspects of insect innate immunity, including these protease cascades and provides basic knowledge that can guide studies of similar systems in insect disease vectors. We have elucidated a part of the M. sexta protease network that activates proPO in response to bacteria and fungi. In this network, recognition proteins bind to microbes and activate the proteases in a cascade mode. We have annotated 193 genes encoding serine proteases and their homologs, identified 36 of the proteins in larval hemolymph, and acquired data indicating that some of them play critical roles in immune signal transduction. Based on the molecular probes, purified proteins and working experience, we propose to investigate two critical steps of the protease network, which are conserved in dipteran species, by combining hemolymph fractionation, recombinant protein production and processing, sequence and expression information, and state-of-the-art mass spectrometry. The specific aims of this project are to: 1) characterize the system initiation by examining interactions of peptidoglycans, two recognition proteins, and hemolymph protease-14 precursor (proHP14) at the domain level; 2) identify 1−2 proHP6-activating proteases and elucidate their activation mechanisms. New knowledge gained in this project will improve understanding of insect immunity at a biochemical level and stimulate related research in vector species.

项目概要 细胞外丝氨酸蛋白酶及其非催化同源物协调关键防御机制 这包括蚊子对引起的病原体和寄生虫的反应。 严重的人类疾病。蛋白水解会产生活性酚氧化酶（PO）、硫酯。 蛋白质 (TEP)、Spätzle 和其他细胞因子催化活性化学物质的产生。 TEP 隔离并杀死入侵的生物体，调理寄生虫，将其作为消灭目标。 Spätzle 和其他细胞因子触发细胞内信号通路，诱导 抗菌肽和其他防御蛋白 在人类疾病的昆虫媒介中，蛋白酶。 入侵者的蛋白质可能会逃避或破坏网络。 来自生化模型昆虫（如 Manduca sexta）的成分及其相互作用是有用的 为了获得对昆虫先天免疫基本方面的详细分子理解， 包括这些蛋白酶级联，并提供可以指导类似研究的基础知识 我们已经阐明了 M. sexta 蛋白酶网络的一部分 激活 proPO 来响应细菌和真菌 在该网络中，识别蛋白结合。 我们注释了 193 个编码基因。 丝氨酸蛋白酶及其同系物，鉴定了幼虫血淋巴中的 36 种蛋白质，并获得了 数据表明其中一些在免疫信号转导中发挥着关键作用。 分子探针、纯化的蛋白质和工作经验，我们建议研究两个关键的 通过结合血淋巴，在双翅目物种中保守的蛋白酶网络的步骤 分级分离、重组蛋白生产和加工、序列和表达信息、 该项目的具体目标是：1）表征 通过检查肽聚糖、两种识别蛋白的相互作用来启动系统 域水平上的血淋巴蛋白酶 14 前体 (proHP14)；2) 识别 1−2 proHP6 激活蛋白 蛋白酶并阐明其激活机制将在该项目中获得。 提高对生化水平上昆虫免疫的认识，并促进相关研究 矢量物种。

项目成果

Nitric Oxide-Induced Calcineurin A Mediates Antimicrobial Peptide Production Through the IMD Pathway.

一氧化氮诱导的钙调神经磷酸酶 A 通过 IMD 途径介导抗菌肽的产生

• DOI: 10.3389/fimmu.2022.905419
• 发表时间: 2022
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Chen, Kangkang;Wang, Xinyan;Wei, Xiangyi;Chen, Jiaqian;Wei, Youheng;Jiang, Haobo;Lu, Zhiqiang;Feng, Congjing
• 通讯作者: Feng, Congjing

Comparative genomic analysis of the Tribolium immune system.

• DOI: 10.1186/gb-2007-8-8-r177
• 发表时间: 2007
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Zou Z;Evans JD;Lu Z;Zhao P;Williams M;Sumathipala N;Hetru C;Hultmark D;Jiang H
• 通讯作者: Jiang H

A comprehensive analysis of the Manduca sexta immunotranscriptome.

• DOI: 10.1016/j.dci.2012.10.004
• 发表时间: 2013-04
• 期刊: DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
• 影响因子: 2.9
• 作者: Gunaratna, Ramesh T.;Jiang, Haobo
• 通讯作者: Jiang, Haobo

A mechanistic analysis of bacterial recognition and serine protease cascade initiation in larval hemolymph of Manduca sexta.

• DOI: 10.1016/j.ibmb.2022.103818
• 发表时间: 2022-09
• 期刊: INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
• 影响因子: 3.8
• 作者: Wang, Yang;Kanost, Michael R.;Jiang, Haobo
• 通讯作者: Jiang, Haobo

The Micrococcus luteus infection activates a novel melanization pathway of cSP10, cSP4, and cSP8 in Helicoverpa armigera.

• DOI: 10.1016/j.ibmb.2022.103775
• 发表时间: 2022-04
• 期刊: Insect biochemistry and molecular biology
• 影响因子: 3.8
• 作者: Qianran Wang;Mengyi Yin;Chuanfei Yuan;Xi-Juan Liu;Haobo Jiang;Manli Wang;Z. Zou;Zhìhóng Hú