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ETR1 Integrates Response to Ethylene and Cytokinins into a Single Multistep Phosphorelay Pathway to Control Root Growth

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Molecular Plant 2019年第10期12卷 1338-1352页

作者： Marketa Zdarska Abigail Rubiato Cuyacot Paul TTarr Amel Yamoune Agnieszka Szmitkowska Vendula Hrdinová Zuzana Gelová Elliot MMeyerowitz Jan Hejátko Functional Genomics and Proteomics of Plants Central European Institute of Technology and National Centre for Biomolecular ResearchMasaryk UniversityCETEC-MUKamenice 5/A262500 BrnoCzech Republic howard hughes medical institute California Institute of Technology1200 East California BoulevardPasadenaCA 91125USA division of biology and biological engineering 156-29 California Institute of Technology1200 East California BoulevardPasadenaCA 91125USA

Cytokinins and ethylene control plant development via sensors from the histidine kinase(HK)***,downstream signaling pathways for the key phytohormones are *** we report that not only cytokinin but also ethylene is able to control root apical meristem(RAM)size through activation of the multistep phosphorelay(MSP)*** found that both cytokinin and ethylene-dependent RAM shortening requires ethylene binding to ETR1 and the HK activity of *** receiver domain of ETR1 interacts with MSP signaling intermediates acting downstream of cytokinin receptors,further substantiating the role of ETR1 in MSP *** revealed that both cytokinin and ethylene induce the MSP in similar and distinct cell types with ETR1-mediated ethylene signaling controlling MSP output specifically in the root transition *** identified members of the MSP pathway specific and common to both hormones and showed that ETR1-regulated ARR3 controls RAM ***1-mediated MSP spatially differs from canonical CTR1/EIN2/EIN3 ethylene signaling and is independent of EIN2,indicating that both pathways can be spatially and functionally ***,we demonstrated that canonical ethylene signaling controls MSP responsiveness to cytokinin specifically in the root transition zone,presumably via regulation of ARR10,one of the positive regulators of MSP signaling in Arabidopsis.

关键词： cytokinin ethylene crosstalk signaling root development

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Crystal structure of HLA-B^(*)5801 with a TW10 HIV Gag epitope reveals a novel mode of peptide presentation

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Cellular & Molecular Immunology 2017年第7期14卷 631-634页

作者： Xiaolong Li Pedro A Lamothe Bruce D Walker Jia-huai Wang Department of medical Oncology and Cancer biology Dana-Farber Cancer InstituteHarvard Medical SchoolBostonMA 02215USA Ragon institute of Massachusetts General Hospital Massachusetts Institute of TechnologyHarvard UniversityBostonMA 02139USA howard hughes medical institute Chevy ChaseMD 20815USA institute for medical and engineering Sciences Massachusetts Institute of TechnologyCambridgeMA 02139USA Department of Pediatrics and Department of biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02215USA

The major histocompatibility complex(MHC)is encoded by a set of genes that play a key role in the vertebrate adaptive immune *** humans,these genes encode proteins termed human leukocyte antigens(HLAs).

关键词： leukocyte antigens Crystal

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Uridylation and adenylation of RNAs

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Science China(Life Sciences) 2015年第11期58卷 1057-1066页

作者： SONG JianBo SONG Jun MO BeiXin CHEN XueMei Shenzhen Key Laboratory of Microbial Genetic engineering College of Life Science Shenzhen University Department of Biochemistry and Molecular biology College of Science Jiangxi Agricultural University Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Optoelectronic Engineering Shenzhen University Department of Botany and Plant Sciences Institute of Integrative Genome Biology University of California howard hughes medical institute University of California

The posttranscriptional addition of nontemplated nucleotides to the 3′ ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated addition of uridine or adenosine to the 3′ ends of RNAs occurs in different organisms ranging from algae to humans, and on different kinds of RNAs, such as histone m RNAs, m RNA fragments, U6 sn RNA, mature small RNAs and their precursors etc. These modifications may lead to different outcomes, such as increasing RNA decay, promoting or inhibiting RNA processing, or changing RNA activity. Growing pieces of evidence have revealed that such modifications can be RNA sequence-specific and subjected to temporal or spatial regulation in development. RNA tailing and its outcomes have been associated with human diseases such as cancer. Here, we review recent developments in RNA uridylation and adenylation and discuss the future prospects in this research area.

关键词： Uridylation adenylation miRNA pre-miRNA U6 snRNA histone mRNA rRNA

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Targeted Mutagenesis of Duplicated Genes in Caenorhabditis elegans Using CRISPR-Cas9

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Journal of Genetics and Genomics 2016年第2期43卷 103-106页

作者： Suhong Xu Zhiping Wang Kyung Won Kim Yishi Jin Andrew D.Chisholm division of biological Sciences Section of Cell and Developmental BiologyUniversity of CaliforniaSan Diego9500 Gilman DriveLa JollaCA 92093USA division of biological Sciences Section of NeurobiologyUniversity of CaliforniaSan Diego9500 Gilman DriveLa JollaCA 92093USA howard hughes medical institute University of CaliforniaSan DiegoLa JollaCA 92093USA School of Medicine Zhejiang UniversityHangzhouChina

CRISPR （clustered regularly interspaced short palindromic repeats）-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 genome editing make it ideal for investigating the function of genes in vivo （Hsu et al., 2014）. Gene duplication is a key driver of evolu- tionary novelty （Taylor and Raes, 2004）. However, duplicated genes with near-identical sequences and functional redun- dancy have posed challenges for genetic analysis （Woollard, 2005）. The functions of duplicated genes can be assessed by simultaneous knockdown using homology-based methods such as RNA interference （RNAi）（Tischler et al., 2006）, Generation of double or triple mutants is an alternative way to assess functional redundancy of duplicated genes, However, generation of such compound mutants by forward or reverse genetic methods is time consuming.

关键词： gene Targeted Mutagenesis of Duplicated Genes in Caenorhabditis elegans Using CRISPR-Cas9

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Cytokinins regulate spatially specific ethylene production to control root growth in Arabidopsis

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Plant Communications 2024年第11期5卷 99-115页

作者： Amel Yamoune Marketa Zdarska Thomas Depaepe Anna Rudolfova Jan Skalak Kenneth Wayne Berendzen Virtudes Mira-Rodado Michael Fitz Blanka Pekarova Katrina Leslie Nicolas Mala Paul Tarr Eliska Spackova Lucia Tomovicova Barbora Parizkova Abigail Franczyk Ingrid Kovacova Vladislav Dolgikh Elena Zemlyanskaya Marketa Pernisova Ondrej Novak Elliot Meyerowitz Klaus Harter Dominique Van Der Straeten Jan Hejatko CEITEC(Central European institute of Technology) Masaryk UniversityBrnoCzech Republic National Centre for Biomolecular Research Faculty of ScienceMasaryk UniversityBrnoCzech Republic Laboratory of Functional Plant biology Department of BiologyGhent UniversityGentBelgium Center for Plant Molecular biology University of TübingenTübingenGermany howard hughes medical institute and division of biology and biological engineering California Institute of TechnologyPasadenaCAUSA Faculty of Science PalackýUniversity and Institute of Experimental BotanyThe Czech Academy of SciencesOlomoucCzech Republic institute of Cytology and Genetics Siberian BranchRussian Academy of SciencesNovosibirsk 630090Russia Faculty of Natural Sciences Novosibirsk State UniversityNovosibirsk 630090Russia

Two principal growth regulators,cytokinins and ethylene,are known to interact in the regulation of plant ***,information about the underlying molecular mechanism and positional specificity of cytokinin/ethylene crosstalk in the control of root growth is *** have identified the spatial specificity of cytokinin-regulated root elongation and root apical meristem(RAM)size,both of which we demonstrate to be dependent on ethylene *** of the cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE(IPT)in proximal and peripheral tissues leads to both root and RAM *** contrast,IPT activation in distal and inner tissues reduces RAM size while leaving the root length comparable to that of mock-treated *** show that cytokinins regulate two steps specific to ethylene biosynthesis:production of the ethylene precursor 1-aminocyclopropane-1-carboxylate(ACC)by ACC SYNTHASEs(ACSs)and its conversion to ethylene by ACC OXIDASEs(ACOs).We describe cytokinin-and ethylene-specific regulation controlling the activity of ACSs and ACOs that are spatially discrete along both proximo/distal and radial root *** direct ethylene measurements,we identify ACO2,ACO3,and ACO4 as being responsible for ethylene biosynthesis and ethylene-regulated root and RAM shortening in cytokinin-treated *** interaction between ARABIDOPSIS RESPONSE REGULATOR 2(ARR2),a member of the multistep phosphorelay cascade,and the C-terminal portion of ETHYLENE INSENSITIVE 2(EIN2-C),a key regulator of canonical ethylene signaling,is involved in the cytokinin-induced,ethylene-mediated control of *** propose tight cooperation between cytokinin and ethylene signaling in the spatially specific regulation of ethylene biosynthesis as a key aspect of the hormonal control of root growth.

关键词： cytokinin ethylene ACC SYNTHASE ACC OXIDASE multistep phosphorelay Arabidopsis

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Computational neuroscience:a frontier of the 21st century

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National Science Review 2020年第9期7卷 1418-1422页

作者： Xiao-Jing Wang Hailan Hu Chengcheng Huang Henry Kennedy Chengyu Tony Li Nikos Logothetis Zhong-Lin Lu Qingming Luo Mu-ming Poo Doris Tsao Si Wu Zhaohui Wu Xu Zhang Douglas Zhou Center for Neural Science New York University Center for Neuroscience Key Laboratory of Medical Neurobiology of the Ministry of Health of China School of Medicine Zhejiang University Department of Neuroscience and Department of Mathematics Center for the Neural Basis of Cognition University of Pittsburgh Université Claude Bernard Lyon 1 Inserm Stem Cell and Brain Research Institute U1208 institute of Neuroscience State Key Laboratory of Neuroscience Chinese Academy of SciencesCAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Center for Brain Science and Brain-Inspired Technology division of Arts and Sciences and NYU-ECNU Institute of Cognitive Neuroscience NYU Shanghai School of Biomedical engineering Hainan University Huazhong University of Science and Technology-Suzhou institute for Brainsmatics division of biology and biological engineering California Institute of Technology howard hughes medical institute School of Electronics engineering and Computer Science IDG/Mc Govern Institute for Brain Research PKU-Tsinghua Center for Life SciencesPeking University College of Computer Science and Technology Zhejiang University institute of Brain-Intelligence Science and Technology Zhangjiang Lab School of Mathematical Sciences MOE-LSCand Institute of Natural Sciences Shanghai Jiao Tong University

THEORY IN NEUROSCIENCE The human brain is a biological organ,weighing about three pounds or 1.4 kg,that determines our behaviors, thoughts,emotions and consciousness. Although comprising only 2%of the total body weigh...

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Nestin is a critical prosurvival factor in neural stem/progenitor cells

Nestin is a critical prosurvival factor in neural stem/proge...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Donghyun Park Andy Peng Xiang Frank Fuxiang Mao Noah Walton Bruce T.Lahn howard hughes medical institute Department of Human GeneticsUniversity of ChicagoChicago IL 60637USA Center for Stem Cell biology and Tissue engineering Sun Yat-sen University

＜正＞The intermediate filament protein,nestin,is a widely employed marker of multipotent neural stem/progenitor cells（NSCs）.Recent in vitro studies have implicated nestin in a number of cellular processes,but there is no evidence yet on its in vivo ***,we report the construction and functional characterization of Nestin knockout *** found mat these mice show embryonic lethality,with neuroepithelia of the developing neural tube exhibiting significantly increased *** with this in vivo observation,NSC cultures derived from knockout embryos show dramatically elevated apoptosis but no defects in proliferation or ***,nestin deficiency has no deflectable effect on the integrity of the ***,the knockout of vimentin,while abolishing nestin’s ability to polymerize into intermediate filaments in NSCs,does not lead to any apoptotic *** data demonstrate that nestin is a critical prosurvival factor in NSCs,and that nestin’s prosurvival function is surprisingly uncoupled from its structural involvement in the cytoskeleton.

关键词： nestin intermediate filament apoptosis neural stem cells neural progenitor cells vimentin

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Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA howard hughes medical institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

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Quantifying E2F1 protein dynamics in single cells

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Quantitative biology 2020年第1期8卷 20-30页

作者： Bernard Mathey-Prevot Bao-Tran Parker Carolyn Im Cierra Hong Peng Dong Guang Yao Lingchong You Department of Pharmacology and Cancer biology Duke University School of MedicineDurhamNC 27710USA Duke University School of Medicine DurhamNC 27710USA Molecular and Cellular biology University of ArizonaTucsonAZ 85721USA Department of Biomedical engineering Duke UniversityDurhamNC 27705USA Center for Genomic and Computational biology Duke UniversityDurhamNC 27705USA Department of Molecular Genetics and Microbiology Duke University School of MedicineDurhamNC 27708USA Department of Pediatrics Duke University School of MedicineDurhamNC 27708USA University of North Carolina School of Medicine Chapel HillNC 27516USA Janelia Research Campus Howard Hughes Medical InstituteAshburnVA 20147USA

Background:E2F1 protein,a major effector of the Rb/E2F pathway plays a central role in regulating cell-fate decisions involved in proliferation,apoptosis,and *** expression is highly dynamic and tightly modulated through a combination of transcriptional,translational and posttranslational ***,the mechanisms by which its expression and activity can promote different cellular outcomes remain to be fully *** better document E2F1 expression in live cells,we have engineered a series of fluorescent E2F1 protein reporters that quantitatively capture E2F1 protein ***:Reporter constructs,under the control of the mouse or human E2F1 proximal promoter,were designed to express an E2F1-Venus fusion protein incapable of binding *** addition,constructs either included or excluded the y untranslated region(3fUTR)of the E2F1 *** constructs were introduced into fibroblasts and epithelial cells,and expression of the fusion reporter protein was validated and quantified in single cells using live ***:In all cases,expression of the reporter protein effectively recapitulated the behavior of E2F1 under various conditions,including cell cycle progression and genotoxic *** or little fluorescent signal of the reporter was detected in G〇,but as the cycle progressed,expression of the reporter protein steadily increased in the nucleus,peaking a few hours before cell division,but declining to baseline 2-3 h prior to the onset of *** absence of the E2F13 fUTR in the constructs led to considerably higher steady-state levels of the fusion protein,which although normally regulated,exhibited a slightly less complex dynamic profile during the cell cycle or genotoxic ***,the presence or absence of Rb failed to impact the overall detection and levels of the reporter ***:Our validated E2F1 protein reporters complement nicely other reporters of the Rb/E2F pathway and provide a unique tool to f

关键词： protein E2F1 reporter cell cycle

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Organization of long-range inputs and outputs of frontal cortex for top-down control

Organization of long-range inputs and outputs of frontal cor...

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中国神经科学学会第十二届全国学术会议

作者： Siyu Zhang Min Xu Wei-Cheng Chang Chenyan Ma Johnny Phong Hoang Do Daniel Jeong Tiffany Lei Jiang Lan Fan Yang Dan Discipline of Neuroscience Department of Anatomy Histology and Embryology and Collaborative Innovation Center for Brain Science Shanghai Jiao Tong University School of Medicine institute of Neuroscience State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Institutes for Biological Sciences CAS division of Neurobiology Department of Molecular and Cell Biology Helen Wills Neuroscience Institute Howard Hughes Medical Institute University of California

Long-range projections from the frontal cortex are known to modulate sensory processing in multiple modalities. Although the mouse has become an increasingly important animal model for studying the circuit basis of behavior, the functional organization of its frontal cortical long-range connectivity remains poorly characterized. Here we used virus-assisted circuit mapping to identify the brain networks for top-down modulation of visual, somatosensory and auditory processing. The visual cortex is reciprocally connected to the anterior cingulate area, whereas the somatosensory and auditory cortices are connected to the primary and secondary motor cortices. Anterograde and retrograde tracing identified the cortical and subcortical structures belonging to each network. Furthermore, using new viral techniques to target subpopulations of frontal neurons projecting to the visual cortex versus the superior colliculus, we identified two distinct subnetworks within the visual network. These findings provide an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.

关键词： virus-assisted circuit mapping long-range projections visual network topdown control

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