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Activation of leukotriene B_(4)receptor 1 is a prerequisite for complement receptor 3-mediated antifungal responses of neutrophils

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Cellular & Molecular Immunology 2024年第3期21卷 245-259页

作者： Yan Xin Sihan Xiong Linghong Zhou Xin Lin Institute for Immunology and School of Medicine Tsinghua University100084BeijingChina tsinghua University-peking University center for life sciences 100084BeijingChina Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalFudan UniversityShanghai200040China

Invasive fungal infections are life-threatening,and neutrophils are vital cells of the innate immune system that defend against *** role of LTA4H-LTB_(4)-BLT1 axis in regulation of neutrophil responses to fungal infection remains poorly ***,we demonstrated that the LTA4H-LTB_(4)-BLT1 axis protects the host against Candida albicans and Aspergillus fumigatus,but not Cryptococcus neoformans infection,by regulating the antifungal activity of *** results show that deleting Lta4h or Blt1 substantially impairs the fungal-specific phagocytic capacity of ***,defective activation of the spleen tyrosine kinase(Syk)and extracellular signal-related kinase(ERK1/2)pathways in neutrophils accompanies this ***,BLT1 regulates CR3-mediated,β-1,3-glucan-induced neutrophil phagocytosis,while a physical interaction with CR3 with slight influence on its dynamics is *** findings thus demonstrate that the LTA4H-LTB_(4)-BLT1 axis is essential for the phagocytic function of neutrophils in host antifungal immune response against Candida albicans and Aspergillus fumigatus.

关键词： LTA4H BLT1 Phagocytosis Complement receptor 3 Fungi

Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

Arabidopsis AIP1-1 regulates the organization of apical actin filaments by promoting their turnover in pollen tubes

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Science China(life sciences) 2020年第2期63卷 239-250页

作者： Min Diao Xin Li Shanjin Huang Institute of Botany Chinese Academy of SciencesBeijing 100093China center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China University of Chinese Academy of sciences Beijing 100049China iHuman Institute Shanghai Tech UniversityShanghai 201210China

Apical actin filaments are highly dynamic structures that are crucial for rapid pollen tube growth, but the mechanisms regulating their dynamics and spatial organization remain incompletely understood. We here identify that AtAIP1-1 is important for regulating the turnover and organization of apical actin filaments in pollen tubes. AtAIP1-1 is distributed uniformly in the pollen tube and loss of function of AtAIP1-1 affects the organization of the actin cytoskeleton in the pollen tube. Specifically, actin filaments became disorganized within the apical region of aip1-1 pollen tubes. Consistent with the role of apical actin filaments in spatially restricting vesicles in pollen tubes, the apical region occupied by vesicles becomes enlarged in aip1-1 pollen tubes compared to WT. Using ADF1 as a representative actin-depolymerizing factor, we demonstrate that AtAIP1-1 enhances ADF1-mediated actin depolymerization and filament severing in vitro, although AtAIP1-1 alone does not have an obvious effect on actin assembly and disassembly. The dynamics of apical actin filaments are reduced in aip1-1 pollen tubes compared to WT. Our study suggests that AtAIP1-1 works together with ADF to act as a module in regulating the dynamics of apical actin filaments to facilitate the construction of the unique "apical actin structure" in the pollen tube.

关键词： pollen tube apical actin structure actin dynamics actin turnover ADF AIP1

Microtubule nucleation and dynamic instability in interphase fission yeast

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Journal of Molecular Cell Biology 2019年第11期11卷 941-943页

作者： Xin Liang tsinghua-peking joint center for life sciences School of Life SciencesTsinghua UniversityBeijing 100084China Max-Planck Partner Group School of Life SciencesTsinghua UniversityBeijing 100084China

Microtubules are dynamic cytoskeletal structures essential for shaping cellular architecture and driving cell *** tube-like structure typically comprises 13 protofilaments,each of which is formed of a/p tubulin heterodimers arranged in a head-to-tail manner(Howard,2001).The formation of microtubules primarily contains two *** first process in which soluble dimers start to form a growing microtubule is termed microtubule nucleation(Figure 1A).

关键词： dynamic Figure typically

DNA Topoisomerase 1 Prevents R-loop Accumulation to Modulate Auxin-Regulated Root Development in Rice

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Molecular Plant 2017年第6期10卷 821-833页

作者： Sarfraz Shafiq Chunli Chen Jing Yang Lingling Cheng Fei Ma Emilie Widemann Qianwen Sun center for Plant Biology and tsinghua-peking joint center for life sciences School of Life Sciences Tsinghua University Beijing 100084 China College of life Science and Technology Huazhong Agricultural University Wuhan 430070 China Permanent affiliation: Department of Environmental sciences COMSATS Institute of Information Technology Abbottabad 22060 Pakistan

R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loop accumulation in various biological processes in plants. Here we show that knockdown of OsTOP1 strongly affects rice development, causing defects in root archi- tecture and gravitropism, which are the consequences of misregulation of auxin signaling and transporter genes. We found that R-loops are naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1 is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets the accurate expression levels of auxin-related genes by preventing the overaccumulation of inherent R-loops. Our data reveal R-loops as important factors in polar auxin transport and plant root development, and highlight that OsTOP1 functions as a key to link transcriptional R-loops with plant hormone signaling, provide new in- sights into transcriptional regulation of hormone signaling in plants.

关键词： R-loops DNA TOP1 auxin signaling root development

EARLY FLOWERING IN SHORT DAYS(EFS) regulates the seed size in Arabidopsis

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Science China(life sciences) 2018年第2期61卷 214-224页

作者： Lingling Cheng Sarfraz Shafiq Wei Xu Qianwen Sun center for Plant Biology and Tsinghua-Peking Joint Center for Life Sciences School of Life Sciences Tsinghua University

Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in *** FLOWERING IN SHORT DAYS(EFS)is the major contributor for H3K36 methylation in Arabidopsis and is important for plant ***,we find that EFS is expressed in different stages of embryo morphogenesis,and the efs mutant produces larger embryo that results in enlarged *** analysis reveals that an imprinted gene MOP9.5 is hypomethylated at the promoter region and its expression is derepressed in efs ***9.5 promoter is marked by various epigenetic modifications,and we find that following the increase of H3K36me3,H3K27me3 and H3K9me2 levels are reduced in efs *** data indicates an antagonistic regulation between H3K36me3 and DNA methylation,and/or H3K27me3 at *** results further show that both maternal and paternal EFS alleles are responsible for the seed size regulation,which unraveled a novel function of EFS in plant development.

关键词： DNA methylation EFS histone modifications seed size gene imprinting

Calcium imaging in Arabidopsis pollen cells using G-CaMP5

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Journal of Integrative Plant Biology 2018年第9期60卷 897-906页

作者： Min Diao Xiaolu Qu Shanjin Huang Key Laboratory of Plant Molecular Physiology Institute of BotanyChinese Academy of SciencesBeijing 100093China center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China University of Chinese Academy of sciences Beijing 100049China

Calcium （Ca2 ＋） signaling has been implicated in poJ]en germination and pollen tube growth. To date, however, we still know very little about how exactly Ca2＋ signaling links to various physiological subcellular processes during pollen germination and pollen tube growth. Given that Ca2＋ signaling is tightly related to the cytosolic concentration and dynamics of Ca2＋, it is vital to trace the dynamic changes in Ca＋ levels in order to decode Ca2＋ signaling. Here, we demonstrate that G-CaMP5 serves well as an indicator for monitoring cytosolic Ca2＋ dynamics in pollen cells. Using this probe, we show that cytosolic Ca2＋ changes dramatically during pollen germination, and, as reported previously, Ca2＋ forms a tip-focused gradient in the pollen tube and undergoes oscillation in the tip region during pollen tube growth. In particular, using G-CaMP5 allowed us to capture the dynamic changes in the cytosolic Ca2＋ concentration （[Ca2＋ ]cyt） in pollen tubes in response to various exogenous treatments. Our data suggest that G-CaMP5 is a suitable probe for monitoring the dynamics of [Ca2＋ ]cyt in pollen cells.

关键词： Calcium imaging in Arabidopsis pollen cells using G-CaMP5 MP

Single-molecule FRET studies on interactions between elongation factor 4 (LepA) and ribosomes

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Chinese Chemical Letters 2018年第10期29卷 1503-1508页

作者： Sijia Peng Ruirui Sun Wenjuan Wang Chunlai Chen School of life sciences Tsinghua-Peking Joint Center for Life SciencesBeijing Advanced Innovation Center for Structural BiologyTsinghua University School of life sciences and Technology center for Protein sciences Tsinghua University

Elongation factor 4（EF4） is one of the highly conserved translational GTPases, whose functions are largely unknown. Structures of EF4 bound ribosomal PRE-translocation and POST-translocation complexes have both been visualized. On top of cellular, structural, and biochemical studies, several controversial models have been raised to rationalize functions of EF4. However, how EF4 modulates elongation through its interactions with ribosomes has not been revealed. Here, using single-molecule fluorescence resonance energy transfer assays, we directly captured short-lived EF4·GTP bound ribosomal PRE and POST translocation complexes, which may adopt slightly different conformations from structures prepared using GDP, GDPNP, or GDPCP. Furthermore, we revealed that EF4·GTP severely impairs delivery of aminoacyl-tRNA into the A-site of the ribosome and moderately accelerates translocation. We proposed that functions of EF4 are to slow overall elongation and to stall majority of ribosomes in POST states under stress conditions.

关键词： Ribosome Single-molecule biophysics Translation Fluorescence resonance energy transfer GTPase

Mechanism of actions of Oncocin, a proline- rich antimicrobial peptide, in early elongation revealed by single-molecule FRET

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Protein & Cell 2018年第10期9卷 890-895页

作者： Sijia Peng Mengyi Yang Rui Ning Sun Yang Liu Wenjuan Wang Qiaoran Xi Haipeng Gong Chunlai Chen School of life sciences Tsinghua University Beijing 100084China tsinghua-peking joint center for life sciences Tsinghua Univer-sity Beijing 100084 China Beijing Advanced Innovation center for Structural Biology Ts-inghua University Beijing 100084 China MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084 China Technology center for Protein sciences Tsinghua UniversityBeijing 100084 China

Dear Editor Proline-rich antimicrobial peptides （PrAMPs） are a class of antimicrobial peptides containing a high content of proline residues. PrAMPs selectively target Gram-negative bacteria through special transporters such as SmbA to enter cyto- plasm （Mattiuzzo et al., 2007）. On the other hand, PrAMPs present a low toxicity to mammalian cells, because they cannot effectively penetrate the mammalian cellular mem- brane （Hansen et al., 2012） or they are internalized through an endocytotic process to minimize interaction with cytosolic ribosomes （Tomasinsig et al., 2006）. Therefore, PrAMPs are promising candidates to treat infections and to deliver drugs （Schmidt et al., 2016）.

关键词： AMINOACYL-TRANSFER-RNA PROTEIN-SYNTHESIS MAMMALIAN-CELLS RIBOSOME INHIBITION SELECTION