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DOCK2 regulates antifungal immunity by regulating rac GTPase activity

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Cellular & Molecular Immunology 2022年第5期19卷 602-618页

作者： Xiaojian Ma Xi Tan Bingbing Yu Wanwei Sun Heping Wang Huijun Hu Yanyun Du Ruirui He Ru Gao Qianwen Peng Zhihui Cui Ting Pan Xiong Feng Junhan Wang Chengqi Xu Bin Zhu Wei Liu Chenhui Wang Key Laboratory of Molecular Biophysics of the Ministry of Education National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China Key Laboratory of Molecular Biophysics the Ministry of EducationCollege of Life Science and Technology and Shenzhen CollegeHuazhong University of Science and TechnologyWuhanHubeiChina The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu611731China Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduSichuanChina University-Affiliated Hospital Huazhong University of Science and TechnologyWuhan430074China Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and TechnologyCenter for Human Genome ResearchCardio-X InstituteHuazhong University of Science and TechnologyWuhan430074PR China

Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and *** major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant ***,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic ***,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in ***2-deficient macrophages exhibit decreased rac GTPase(rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling ***,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of rac GTPases and then increases ROS production and downstream signaling ***,nanoparticle-mediated delivery of in vitro transcribed(IVT)rac1 mRNA promotes the activity of rac1 and helps to eliminate fungal infection in *** together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of rac GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.

关键词： DOCK2 rac Anti-fungal immunity IVT-mRNA

Restoring-force model of modified rac columns with silica fume and hybrid fiber

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Journal of Central South University 2017年第11期24卷 2674-2684页

作者：杨涛王社良刘伟 School of Environmental and Chemical Engineering Xi’an Polytechnic UniversityXi’an 710048China School of Civil Engineering Xi’an University of Architecture and TechnologyXi’an 710055China Academy of Building Research of Shaanxi Provincial Xi’an 710082China

In order to establish a restoring-force model for modified concrete columns with recycled aggregates concrete(rac), cyclic loading tests were carried out on five concretes with rac columns and ordinary concrete frame columns under the combined influence with different admixtures and admixtures ratios(silica fume and hybrid fiber). The expressions for characteristic nodes of the skeleton curve were given by the analysis and numerical regression of the test results. In addition, the hysteretic rules of the restoring-force model and the expression for unloading stiffness were presented. Finally, we summed up the complete calculation method of the hysteretic restoring force, whose results were in good agreement with experiment. The results demonstrated that the proposed model could simulate and reflect the corresponding hysteretic behaviors, and the calculation method can provide the theoretical basis for the engineering application.

关键词： modified rac columns skeleton curve unloading stiffness hysteretic rule restoring-force model

Estimated prevalence of Echinococcus multilocularis in rac-coon dogs Nyctereutes procyonoides in northern Branden- burg, Germany

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动物学报：英文版 2011年第5期57卷 655-661页

作者： Sabine SCHWARZ Astrid SUTOR Christoph STAUBACH Roswitha MATTIS Kirsten TACKMANN Franz Josef CONRATHS Friedrich-Loeffier-Institut Federal Research Institute for Animal Health Institute of Epidemiology 16868 Wusterhausen Germany

Human alveolar echinococcosis, caused by the larval stage of the small fox tapeworm, is a lethal zoonotic infection if left untreated.E. multilocularisis distributed in the Northern Hemisphere and lives in the small intestines of carnivores, mainly canids. The main definitive host ofE. multilocularisin European countries is the red foxVulpes vulpesand in the last ten years new endemic areas for the parasite in Central Europe have been identified. In some areas, for instance in Germany, the raccoon dogNyctereutes procyonoides- a spreading neozoon - must be regarded as an additional definitive host forE. multilocularis. In 2001 this parasite was found for the first time in raccoon dogs in the Federal State of Brandenburg, Germany. Between 2000 and 2008, 1,252 raccoon dogs from Brandenburg were examined by the Intestinal Scraping Technique. The majority of samples were obtained in five northern counties and all 60 animals that tested positive forE. multiloculariswere located there. The estimated true prevalence calculated by a beta-binomial- model ranged from 6%–12%.

关键词：犬科动物德国估计 rac 棘球蚴浣熊食肉动物人畜共患病

rac GTPases:domain-specific functions in neuronal development

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Neural Regeneration Research 2019年第8期14卷 1367-1368页

作者： Steffen Norgaard Roger Pocock Development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology Monash University Melbourne Victoria Australia Biotech Research and Innovation Centre University of Copenhagen Copenhagen Denmark

Understanding fundamental mechanisms governing axon outgrowth and guidance can inform the development of therapeutic strategies to restore neuronal function damaged though injury or disease. Axons navigate the extracellular environment by responding to guidance cues that bind to cell surface receptors to relay information intracellularly via Rho GTPase family members, including the rac GTPases.

关键词： rac GTPases domain-specific functions neuronal development

rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells

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Chinese Medical Journal 2004年第8期117卷 1143-1150页

作者：杨水祥闫娟 Shailesh S.Deshpande Kaikobad Irani Charles J.Lowenstein Cardiovascular Center Tongren Hospital Capital University of Medical SciencesBeijing100730China Division of Cardiology Department of Medicine Department of PathologyJohns Hopkins UniversitySchool of MedicineBaltimoreMaryland 21205USA

Background The release of Weibel-Palade Bodies (WPB) is a form of endothelial cell activation But the signal transduction pathway leading to WPB release is not yet defined We hypothesized that small G-protein rac1 and reactive oxygen species (ROS) mediate the ligand induced release of Weibel-Palade Bodies Methods We tested this hypothesis by using wild-type and mutant adenoviral rac1 expression vectors, and by manipulating the production and destruction of superoxide and hydrogen peroxide in human aortic endothelial cells (HAEC) KH*2/5DResults Thrombin (1 0 Unit, 30 min) induced the increase of WPB release by 3 7-fold in HAEC, and that H 2O 2 (0 1 mmol/L, 30 min) induced by 4 5-fold These results correlated with thrombin-stimulated activation of rac-GTP binding activity by 3 5-fold, and increase of ROS production by 3 4-fold The dominant negative adenoviral rac-N17 gene transfer dramatically inhibited the release of WPB by 64 2% (control) and 77 3% (thrombin-stimulation), and decreased ROS production by 65 5% (control) and 83 6% (thrombin-stimulation) compared with non-infected cells, respectively Anti-oxidants, catalase and N-acetyl-cysteine significantly decreased the release of WPB by 34% and 79% in control cells, and further decreased by 63 6% and 46 7% in rac-N17 transferred cells compared with non-infected cells We also confirmed that rac1 was located upstream of ROS in the WPB release pathway KH*2/5DConclusions Small G-protein rac1 medicates ligand-induced release of Weibel-Palade Bodies in human aortic endothelial cells, and the signal pathway of WPB release is a rac1-dependent ROS regulating mechanism

关键词： Weibel-Palade Bodies von Willebrand factor P-selectin rac thrombin exocytosis reactive oxygen species

1，2－Cyclic　Monoalkly－rac－Glycerothiophosphates　of　2＇，3＇－O－Isopropylideneuridine

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Chinese Chemical Letters 1996年第9期7卷 799-800页

作者： Huan Ming CHEN Ru Yu CHEN Ping Ying LI Cheng Xiang ZHANG(Institute of Elemento-Organic Chemisty,Institute of Polymer Chemistry,Nankai University,Tianjin,30O071) Inst. of Elemento-Organic Chemistry Nankai University Tianjin 300071 Institute of Polymer Chemistry Nankai University Tianjin 300071

A series of 1,2-cyclic monoalkyl-rac-glycerothiophsphates of 2'3'-O- isopropylideneuridine were synthesized in a one-pot procedure in overall yield of 36-40% by means of hexaethylphosphorous triamide as phosphorylatin... 详细信息

关键词：梗梗 rac 桑桑 Glycerothiophosphates Isopropylideneuridine Monoalkly Cyclic

Forgetting and small G protein rac

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Protein & Cell 2010年第6期1卷 503-506页

作者： Yichun Shuai Yi Zhong School of Life Sciences Tsinghua UniversityBeijing 100084China Cold Spring Harbor Laboratory Cold Spring HarborNY 11724USA

It is far from understood why we forget things that are known to us seconds *** evidence emphasizes that small G protein rac could be a key to understanding this type of rapid early memory *** current perspective article will first review these studies and then discuss their implications for the internal processes underlying forgetting.

关键词： forget getting rac

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rac小G蛋白与中性粒细胞趋化研究进展

中国药理学通报 2010年第11期26卷 1407-1409页

作者：姚红伊颜小锋吴希美浙江大学医学院附属第二医院药剂科浙江杭州310009 浙江大学医学院呼吸药物研究实验室浙江杭州310058

Rho家族小G蛋白(Rho Small GTPase)作为"分子开关",不仅调控细胞骨架,而且参与调节细胞周期、细胞运动、生长、黏附、基因转录和信号转导。rac GTPase是其主要的家族成员之一,该文通过rac GTPase影响中性粒细胞极化、黏附、跨膜、迁移... 详细信息

Rho家族小G蛋白(Rho Small GTPase)作为"分子开关",不仅调控细胞骨架,而且参与调节细胞周期、细胞运动、生长、黏附、基因转录和信号转导。rac GTPase是其主要的家族成员之一,该文通过rac GTPase影响中性粒细胞极化、黏附、跨膜、迁移及血管内皮细胞通透性调控中性粒细胞趋化,研究其在中性粒细胞介导的炎症过程中发挥的重要作用。

关键词： rac 中性粒细胞趋化迁移 NADPH氧化酶细胞骨架内皮细胞通透性

rac1和rac2参与调节人单核细胞趋化和NADPH氧化酶活性

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中国生物化学与分子生物学报 2011年第9期27卷 858-863页

作者：谭运年成海恩金亚平浙江大学医学院附属第二医院生化室杭州310009

为了探讨小分子GTP酶蛋白rac1和rac2在人单核细胞中趋化迁移以及还原型辅酶II(NADPH)氧化酶活性中的作用,采用小分子干扰siRNA对人单核细胞中rac1、rac2分别进行特异性抑制,采用实时定量PCR技术、免疫印迹技术在RNA和蛋白质水平上确认... 详细信息

为了探讨小分子GTP酶蛋白rac1和rac2在人单核细胞中趋化迁移以及还原型辅酶II(NADPH)氧化酶活性中的作用,采用小分子干扰siRNA对人单核细胞中rac1、rac2分别进行特异性抑制,采用实时定量PCR技术、免疫印迹技术在RNA和蛋白质水平上确认抑制效果,使用甲酰三肽(formyl-met-leu-phe,fMLP)、人单核细胞趋化因子(monocyte chemoattractant protein-1,MCP-1)诱导单核细胞趋化;用血清调理的酵母多糖(serum opsonized zymosan,ZOP)、佛波酯(phosphomolybdic acid,PMA)激活单核细胞NADPH氧化酶活性,诱导活性氧(Reactive oxygenspecies,ROS)产生,以此对rac1和rac2作用进行研究.结果表明,小分子干扰siRNA能够在mRNA水平和蛋白质水平分别有效抑制目的基因表达;使用Chamber assay方法发现,仅rac1参与了fMLP、MCP-1诱导的人单核细胞趋化.rac激活实验确证,rac1参与MCP-1诱导的趋化;细胞色素C还原法表明,rac1和rac2均参与PMA和ZOP诱导人单核细胞ROS生成.在人单核细胞中,rac1和rac2基因沉默模型的成功建立以及初步研究显示,rac1和rac2的不同作用结果将为深入研究它们在人单核细胞中的功能奠定了良好基础.

关键词：单核细胞 rac 小干扰RNA 趋化活性氧