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NADPH oxidase family proteins:signaling dynamics to disease management

Cellular & Molecular Immunology 2022年第6期19卷 660-686页

作者： Rizwana Begum Shilpa Thota Abubakar Abdulkadir Gagandeep Kaur Prathyusha Bagam Sanjay Batra present address:department of Environmental Medicine University of RochesterSchool of Medicine and DentistryRochesterNY14642USA Laboratory of Pulmonary Immunotoxicology Department of Environmental ToxicologySouthern University and A&M CollegeBaton RougeLA70813USA present address:Division of Systems biology National Center for Toxicological ResearchJeffersonAR72079USA

Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologies due to excessive inflammation.Professional phagocytes such as neutrophils(PMNs),eosinophils,monocytes,and macrophages use superoxide-generating NADPH oxidase(NOX)as part of their arsenal of antimicrobial mechanisms to produce high levels of ROS.NOX is a multisubunit enzyme complex composed of five essential subunits,two of which are localized in the membrane,while three are localized in the cytosol.In resting phagocytes,the oxidase complex is unassembled and inactive;however,it becomes activated after cytosolic components translocate to the membrane and are assembled into a functional oxidase.The NOX isoforms play a variety of roles in cellular differentiation,development,proliferation,apoptosis,cytoskeletal control,migration,and contraction.Recent studies have identified NOX as a major contributor to disease pathologies,resulting in a shift in focus on inhibiting the formation of potentially harmful free radicals.Therefore,a better understanding of the molecular mechanisms and the transduction pathways involved in NOX-mediated signaling is essential for the development of new therapeutic agents that minimize the hyperproduction of ROS.The current review provides a thorough overview of the various NOX enzymes and their roles in disease pathophysiology,highlights pharmacological strategies,and discusses the importance of computational modeling for future NOX-related studies.

关键词： NADPH oxidase Reactive oxygen species Inflammation Inhibitors In silico

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入侵植物根茎的生长和竞争力因相邻植物的不同而不同

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Journal of Plant Ecology 2021年第4期14卷 638-647页

作者： Alyssa Laney Smith Daniel Z.Atwater Wonjae Kim David C.Haak Jacob N.Barney School of Plant and Environmental Sciences Virginia TechBlacksburgVAUSA department of biology Earlham CollegeRichmondINUSA present address:department of Ecology and Evolutionary biology University of ArizonaTucsonAZUSA

物种内的遗传和表型变异对进化过程的影响已众所周知,但人们对种内变异如何影响群落水平过程还知之甚少。在人类对自然系统造成影响的大背景下,由于人类活动可能会产生巨大的选择压力,因此具有生态意义的种内变异可能会特别重要。在一... 详细信息

物种内的遗传和表型变异对进化过程的影响已众所周知,但人们对种内变异如何影响群落水平过程还知之甚少。在人类对自然系统造成影响的大背景下,由于人类活动可能会产生巨大的选择压力,因此具有生态意义的种内变异可能会特别重要。在一项温室实验中,我们研究了一种分布广泛的入侵物种和农业杂草石茅(Sorghum halepense)在受到种间竞争、种内竞争和土壤肥力的影响时,其在生物量和根茎方面发生的种内变异和生态型变异。与我们的预期和此前的研究结果不同的是,我们并没有在这一早期生命阶段中发现石茅各生态型生物量的改变。然而,我们确实发现石茅的生物量会随着竞争植株种类和土壤施肥方式的不同而发生很显著的变化,同时不同株之间也存在很大差异。农业生态型的根茎较其它生态型大了11%,经施肥处理后的增大幅度更高至3倍;虽然施肥后的根茎生物量增加了~50%,但生态型之间却并无差异。有趣的是,当受到种内竞争时,与玉米(Zea mays)发生种间竞争时的情况相比,石茅的生物量和根茎生物量产出分别减少了32%和20%。我们的研究结果表明,针对相邻植株的种类而发生的物种特异性竞争响应以及根茎分配的改变,石茅在受竞争时可能会产生适应性响应,从而使分配情况发生改变。

关键词：适应农业竞争外来入侵选择石茅(Sorghum halepense)

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The WAK-like protein RFO1 acts as a sensor of the pectin methylation status in Arabidopsis cell walls to modulate root growth and defense

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Molecular Plant 2023年第5期16卷 865-881页

作者： Apolonio I.Huerta Gloria Sancho-Andre´s Juan Carlos Montesinos Javier Silva-Navas Sole`ne Bassard Corinne Pau-Roblot Christopher Kesten Rudolf Schlechter Susanne Dora Temurkhan Ayupov Je´rome Pelloux^ Julia Santiago Clara Sa´nchez-Rodrı´guez ETH Zurich Institute of Molecular Plant Biology(D-BIOL)ZurichSwitzerland University of Lausanne Department of Plant Molecular BiologyLausanneSwitzerland UMRT INRAE 1158 BioEcoAgro–BIOPI Biologie des Plantes et Innovation Universite´de Picardie33 Rue St Leu80039 AmiensFrance present address:Lonza AG VispVisSwitzerland present address:Institute of Microbiology Freie Universitat BerlinBerlinGermany present address:Institute of Molecular and Clinical Ophthalmology-Basel BaselSwitzerland present address:Centro de Biotecnologı´a y Geno´mica de Plantas Universidad Polite´cnica de Madrid(UPM)–Instituto Nacional de Investigacio´n y Tecnologı´a Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPM28223 Pozuelo de Alarco´nSpain

Most organisms adjust their development according to the environmental conditions.For the majority,this implies the sensing of alterations to cell walls caused by different cues.Despite the relevance of this process,few molecular players involved in cell wall sensing are known and characterized.Here,we show that the wall-associated kinase-like protein RESISTANCE TO FUSARIUM OXYSPORUM 1(RFO1)is required for plant growth and early defense against Fusarium oxysporum and functions by sensing changes in the pectin methylation levels in the cell wall.The RFO1 dwell time at the plasma membrane is affected by the pectin methylation status at the cell wall,regulating MITOGEN-ACTIVATED PROTEIN KINASE and gene expression.We show that the extracellular domain of RFO1 binds de-methylated pectin in vitro,whose distribution in the cell wall is altered during F.oxysporum infection.Further analyses also indicate that RFO1 is required for the BR-dependent plant growth alteration in response to inhibition of pectin de-methyl-esterase activity at the cell wall.Collectively,our work demonstrates that RFO1 is a sensor of the pectin methylation status that plays a unique dual role in plant growth and defense against vascular pathogens.

关键词： alterations walls pectin

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Translational Regulation of Metabolic Dynamics during Effector-Triggered Immunity

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Molecular Plant 2020年第1期13卷 88-98页

作者： Heejin Yoo George H.Greene Meng Yuan Guoyong Xu Derek Burton Lijing Liu Jorge Marques Xinnian Dong Howard Hughes Medical Institute Department of BiologyDuke UniversityBox 90338DurhamNC 27708USA National Key Laboratory of Crop Genetic Improvement National Centre of Plant Gene Research(Wuhan)Huazhong Agricultural University430070 WuhanChina present address:department of Plant biology Ecologyand EvolutionOklahoma State UniversityStillwaterOK 74078USA present address:National Key Laboratory of Hybrid Rice Institute for Advanced Studies(IAS)Wuhan UniversityWuhanHubei 430072China present address:Key Laboratory of Plant Development and Environment Adaptation biology Ministry of EducationSchool of Life SciencesShandong UniversityQingdaoChina present address:David H.Murdock Research Institute KannapolisNC 28081USA

Recent studies have shown that global translational reprogramming is an early activation event in pattern-triggered immunity,when plants recognize microbe-associated molecular patterns.However,it is not fully known whether translational regulation also occurs in subsequent immune responses,such as effector-triggered immunity(ETI).In this study,we performed genome-wide ribosome profiling in Arabidopsis upon RPS2-mediated ETI activation and discovered that specific groups of genes were translationally regulated,mostly in coordination with transcription.These genes encode enzymes involved in aromatic amino acid,phenylpropanoid,camalexin,and sphingolipid metabolism.The functional significance of these components in ETI was confirmed by genetic and biochemical analyses.Our findings provide new insights into diverse translational regulation of plant immune responses and demonstrate that translational coordination of metabolic gene expression is an important strategy for ETI.

关键词： translational regulation ribosome profiling effector-triggered immunity,ETI phenylalanine phenylpropanoids helper receptors

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Inhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy

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Journal of Molecular Cell biology 2020年第9期12卷 700-712页

作者： Daniel Nguyen Kun Yang Lucia Chiao Yun Deng Xiang Zhou Zhen Zhang Shelya X.Zeng Hua Lu department of Biochemistry and Molecular biology Tulane Cancer CenterTulane University School of MedicineNew OrleansLA 70112USA department of Radiation Oncology Shanghai Cancer CenterDepartment of OncologyShanghai Medical SchoolFudan UniversityShanghai 200032China present address:Verna and Marrs McLean department of Biochemistry and Molecular biology Baylor College of MedicineHoustonTX 77030USA present address:department of Radiation Oncology Shanghai Cancer CenterFudan UniversityShanghai 200032China present address:Institute of Biomedical Sciences Shanghai Cancer CenterFudan UniversityShanghai 200032China

The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy(CMA)pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.

关键词： p73 NGFR chaperone-mediated autophagy Lamp2a HSPA8

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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer Institute BostonMA 02215USA present address:Massachusetts Institute of Technology BostonMA 02139USA present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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Conservation and Diversification of the SHR-SCR- SCL23 Regulatory Network in the Development of the Functional Endodermis in Arabidopsis Shoots

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Molecular Plant 2016年第8期9卷 1197-1209页

作者： Eun Kyung Yoon Souvik Dhar Mi-Hyun Lee Jae Hyo Song Shin Ae Lee Gyuree Kim Sejeong Jang Ji Won Choi Jeong-Eun Choe Jeong Hoe Kim Myeong Min Lee Jun Lim department of Systems Biotechnology Konkuk University Seoul 05029 Korea department of Systems biology Yonsei University Seoul 03722 Korea department of biology Kyungpook National University Daegu 41566 Korea 4TheSe tlRors cotribCited equally/to ttats article present address: department of Agricultural Biotechnology National Institute of Agricultural Sciences Jeonju 54874 Korea present address: department of Agricultural biology National Institute of Agricultural Sciences Wanju 55365 Korea

Development of the functional endodermis of Arabidopsis thaliana roots is controlled, in part, by GRAS transcription factors, namely SHORT-ROOT （SHR）, SCARECROW （SCR）, and SCARECROW-LIKE 23 （SCL23）. Recently, it has been shown that the SHR-SCR-SCL23 regulatory module is also essential for spec- ification of the endodermis （known as the bundle sheath） in leaves. Nevertheless, compared with what is known about the role of the SHR-SCR-SCL23 regulatory network in roots, the molecular interactions of SHR, SCR, and SCL23 are much less understood in shoots. Here, we show that SHR forms protein com- plexes with SCL23 to regulate transcription of SCL23 in shoots, similar to the regulation mode of SCR expression. Our results indicate that SHR acts as master regulator to directly activate the expression of SCR and SCL23. In the SHR-SCR-SCL23 network, we found a previously uncharacterized negative feed- back loop whereby SCL23 modulates SHR levels. Through molecular, genetic, physiological, and morpho- logical analyses, we also reveal that the SHR-SCR-SCL23 module plays a key role in the formation of the endodermis （known as the starch sheath） in hypocotyls. Taken together, our results provide new insights into the regulatory role of the SHR-SCR-SCL23 network in the endodermis development in both roots and shoots.

关键词： endodermis gene regulatory network SHORT-ROOT SCARECROW SCARECROW-LIKE 23,transcription factor

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Functional Analysis of Semi-conserved Transit Peptide Motifs and Mechanistic Implications in Precursor Targeting and Recognition

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Molecular Plant 2016年第9期9卷 1286-1301页

作者： Kristen Holbrook Chitra Subramanian Prakitchai Chotewutmontri L. Evan Reddick Sarah Wright Huixia Zhang Lily Moncrief Barry D. Bruce department of Biochemistry Cellular and Molecular Biology Graduate Program in Plant Physiology and Genetics Graduate School of Genome Science and Technology department of Botany department of BotanyUniversity of Tennessee Knoxville TN 37996 USA present address: department of Infectious Disease St. Jude Children's Research Hospital Memphis TN 38105 USA present address: Institute of Molecular biology University of Oregon Eugene OR 97403 USA present address: department of Microbiology University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas TX 75390 USA present address: Albert R. Mann Library Cornell University Ithaca NY 14850 USA present address: U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring MD 20993 USA

Over 95% of plastid proteins are nuclear-encoded as their precursors containing an N-terminal extension known as the transit peptide （TP）. Although highly variable, TPs direct the precursors through a conserved, posttranslational mechanism involving translocons in the outer （TOC） and inner envelope （TOC）. The organelle import specificity is mediated by one or more components of the Toc complex. However, the high TP diversity creates a paradox on how the sequences can be specifically recognized. An emerging model of TP design is that they contain multiple loosely conserved motifs that are recognized at different steps in the targeting and transport process. Bioinformatics has demonstrated that many TPs contain semiconserved physicochemical motifs, termed FGLK. In order to characterize FGLK motifs in TP recognition and import, we have analyzed two well-studied TPs from the precursor of RuBisCO small subunit （SStp） and ferredoxin （Fdtp）. Both SStp and Fdtp contain two FGLK motifs. Analysis of large set mutations （-85） in these two motifs using in vitro, in organello, and in vivo approaches support a model in which the FGLK domains mediate interaction with TOC34 and possibly other TOC components. In vivo import analysis suggests that multiple FGLK motifs are functionally redundant. Furthermore, we discuss how FGLK motifs are required for efficient precursor protein import and how these elements may permit a convergent function of this highly variable class of targeting sequences.

关键词： chloroplast biology protein translocation Toc34 transit peptide cell biology

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Acorn size and tolerance to seed predators:the multiple roles of acorns as food for seed predators,fruit for dispersal and fuel for growth

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Integrative Zoology 2018年第3期13卷 251-266页

作者： Andrew W.BARTLOW Salvatore JAGOSTA Rachel CURTIS Xianfeng YI Michael ASTEELE department of biology and The WIESS Institute for Environmental Science and Sustainability Wilkes UniversityWilkes BarrePennsylvaniaUSA Present address:Department of Biology University of UtahSalt Lake CityUtahUSA Center for Environmental Studies and department of biology Virginia Commonwealth UniversityRichmondVirginiaUSA present address:department of Veterinary Integrative Biosciences Texas A&M UniversityCollege StationTexasUSA College of Life Sciences Jiangxi Normal UniversityNanchangJiangxiChina.

Fitness of parents and offspring is affected by offspring size.In oaks(Quercus spp.),acorns vary considerably in size across,and within,species.Seed size influences dispersal and establishment of oaks,but it is not known whether size imparts tolerance to seed predators.Here,we examine the relative extent to which cotyledon size serves as both a means for sustaining partial consumption and energy reserves for developing seedlings during early stages of establishment.Acorns of 6 oak species were damaged to simulate acorn predation by vertebrate and invertebrate seed predators.Seedling germination/emergence and growth rates were used to assess seedling performance.We predicted that if cotyledons are important for dispersal,acorns should show tolerance to partial seed consumption.Alternatively,if the cotyledon functions primarily as an energy reserve,damage should significantly influence seedling performance.Acorns of each species germinated and produced seedlings even after removing>50%of the cotyledon.Seed mass explained only some of the variation in performance.Within species,larger acorns performed better than smaller acorns when damaged.Undamaged acorns performed as well or better than damaged acorns.There was no pattern among individual species with increasing amounts of damage.In some species,simulated invertebrate damage resulted in the poorest performance,suggesting alternative strategies of oaks to sustain damage.Large cotyledons in acorns may be important for attracting seed dispersers and sustaining partial damage,while also providing energy to young seedlings.Success of oak establishment may follow from the resilience of acorns to sustain damage at an early stage.

关键词： acorns damage tolerance dispersal Quercus seed size

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A Plant SMALL RNA-BINDING PROTEIN 1 Family Mediates Cell-to-Cell Trafficking of RNAi Signals

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Molecular Plant 2020年第2期13卷 321-335页

作者： Yan Yan Byung-Kook Ham Yee Hang Chong Shyi-Dong Yeh William J.Lucas department of Plant biology College of Biological SciencesUniversity of CaliforniaDavisCA 95616USA department of Plant Pathology National Chung-Hsing UniversityTaichung present address:Global Institute for Food Security University of SaskatchewanSaskatoonSK S7N 4J8Canada Present address:Department of Biology University of Saskatchewan112 Science PlaceSaskatoonSK S7N 5E2Canada

In plants,RNA interference(RNAi)plays a pivotal role in growth and development,and responses to environmental inputs,including pathogen attack.The intercellular and systemic trafficking of small interfering RNA(siRNA)/microRNA(miRNA)is a central component in this regulatory pathway.Currently,little is known with regards to the molecular agents involved in the movement of these si/miRNAs.To address this situation,we employed a biochemical approach to identify and characterize a conserved SMALL RNA-BINDING PROTEIN 1(SRBP1)family that mediates non-cell-autonomous small RNA(sRNA)trafficking.In Arabidopsis,AtSRBP1 is a glycine-rich(GR)RNA-binding protein,also known as AtGRP7,which we show binds single-stranded siRNA.A viral vector,Zucchini yellow mosaic virus(ZYMV),was employed to functionally characterized the AtSRBP1-4(AtGRP7/2/4/8)RNA recognition motif and GR domains.Cellular-based studies revealed the GR domain as being necessary and sufficient for SRBP1 cell-to-cell movement.Taken together,our findings provide a foundation for future research into the mechanism and function of mobile sRNA signaling agents in plants.

关键词： RNAi small RNA-binding protein family small RNA movement non-cell-autonomous protein glycinerich protein

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