archive-com.com » COM » C » CELL-RESEARCH.COM

Total: 1754

Choose link from "Titles, links and description words view":

Or switch to "Titles and links view".
  • Cell Research
    Medicine Peking University Beijing 100871 China 2 College of Engineering Peking University Beijing 100871 China 3 State Key Laboratory of Natural and Biomimetic Drugs Peking University Beijing 100871 China Correspondence Jianzhong Xi Jing Wei Xiong Tel 86 10 6276 0698 86 10 6276 6239 E mail jzxi pku edu cn jingwei xiong pku edu cn Recent advances with the type II clustered regularly interspaced short palindromic repeats CRISPR system promise an improved approach to genome editing However the applicability and efficiency of this system in model organisms such as zebrafish are little studied Here we report that RNA guided Cas9 nuclease efficiently facilitates genome editing in both mammalian cells and zebrafish embryos in a simple and robust manner Over 35 of site specific somatic mutations were found when specific Cas gRNA was used to target either etsrp gata4 or gata5 in zebrafish embryos in vivo The Cas9 gRNA efficiently induced biallelic conversion of etsrp or gata5 in the resulting somatic cells recapitulating their respective vessel phenotypes in etsrpy11 mutant embryos or cardia bifida phenotypes in fautm236a mutant embryos Finally we successfully achieved site specific insertion of mloxP sequence induced by Cas9 gRNA system in zebrafish embryos These results demonstrate that

    Original URL path: http://www.cell-research.com/arts.asp?id=1642 (2016-02-14)
    Open archived version from archive

  • Cell Research
    Medicine II Albert Ludwigs University Freiburg Germany 3 Department of Biomedical Engineering University of Texas at Arlington Arlington TX 76019 USA 4 Department of Developmental Biology University of Texas Southwestern Medical Center Dallas TX 75390 USA 5 Center for Molecular Neurobiology Hamburg Germany 6 Clinic for Gastroenterology Hepatology and Infectiology Heinrich Heine University Düsseldorf Moorenstrasse 5 D 40225 Düsseldorf Germany 7 Department of Molecular Genetics University of Texas Southwestern Medical Center Dallas TX 75390 USA 8 Present address Roche Pharma AG D 79639 Grenzach Wyhlen Germany Correspondence Hans H Bock Tel 49 761 203 8421 E mail hans bock zfn uni freiburg de HansHenrich Bock med uniduesseldorf de The integration of newborn neurons into functional neuronal networks requires migration of cells to their final position in the developing brain the growth and arborization of neuronal processes and the formation of synaptic contacts with other neurons A central player among the signals that coordinate this complex sequence of differentiation events is the secreted glycoprotein Reelin which also modulates synaptic plasticity learning and memory formation in the adult brain Binding of Reelin to ApoER2 and VLDL receptor two members of the LDL receptor family initiates a signaling cascade involving tyrosine phosphorylation of the intracellular cytoplasmic adaptor protein Disabled 1 which targets the neuronal cytoskeleton and ultimately controls the positioning of neurons throughout the developing brain However it is possible that Reelin signals interact with other receptor mediated signaling cascades to regulate different aspects of brain development and plasticity EphB tyrosine kinases regulate cell adhesion and repulsion dependent processes via bidirectional signaling through ephrin B transmembrane proteins Here we demonstrate that Reelin binds to the extracellular domains of EphB transmembrane proteins inducing receptor clustering and activation of EphB forward signaling in neurons independently of the classical Reelin receptors ApoER2 and VLDLR Accordingly mice

    Original URL path: http://www.cell-research.com/arts.asp?id=1643 (2016-02-14)
    Open archived version from archive

  • Cell Research
    3 1 Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education Department of Biochemistry and Molecular Biology Peking University Health Science Center Beijing 100191 China 2 State Key Laboratory of Oncology in South China Sun Yat Sen University Cancer Center Guangzhou Guangdong 510060 China 3 Peking Tsinghua University Center for Life Sciences Peking University Beijing 100871 China Correspondence Wei Guo Zhu Ying Zhao Tel 86 10 82802235 86 10 82802235 E mail zhuweiguo bjmu edu cn zhaoying0812 bjmu edu cn Autophagy is activated to maintain cellular energy homeostasis in response to nutrient starvation However autophagy is not persistently activated which is poorly understood at a mechanistic level Here we report that turnover of FoxO1 is involved in the dynamic autophagic process caused by glutamine starvation X box binding protein 1u XBP 1u has a critical role in FoxO1 degradation by recruiting FoxO1 to the 20S proteasome In addition the phosphorylation of XBP 1u by extracellular regulated protein kinases1 2 ERK1 2 on Ser61 and Ser176 was found to be critical for the increased interaction between XBP 1u and FoxO1 upon glutamine starvation Furthermore knockdown of XBP 1u caused the sustained level of FoxO1 and the persistent activation of

    Original URL path: http://www.cell-research.com/arts.asp?id=1644 (2016-02-14)
    Open archived version from archive

  • Cell Research
    Swee Hock School of Public Health National University of Singapore Singapore 117597 2 NUS Graduate School for Integrative Sciences and Engineering National University of Singapore Singapore 117597 3 Microscopy Facility IFR 141 IPSIT rue JB Clément 92296 Châtenay Malabry France 4 University Paris Sud Orsay France 5 INSERM U984 92296 Châtenay Malabry France 6 Reed College Portland OR 97202 USA Correspondence Han Ming Shen E mail han ming shen nuhs edu sg Lysosome is a key subcellular organelle in the execution of the autophagic process and at present little is known whether lysosomal function is controlled in the process of autophagy In this study we first found that suppression of mammalian target of rapamycin mTOR activity by starvation or two mTOR catalytic inhibitors PP242 and Torin1 but not by an allosteric inhibitor rapamycin leads to activation of lysosomal function Second we provided evidence that activation of lysosomal function is associated with the suppression of mTOR complex 1 mTORC1 but not mTORC2 and the mTORC1 localization to lysosomes is not directly correlated to its regulatory role in lysosomal function Third we examined the involvement of transcription factor EB TFEB and demonstrated that TFEB activation following mTORC1 suppression is necessary but not

    Original URL path: http://www.cell-research.com/arts.asp?id=1645 (2016-02-14)
    Open archived version from archive

  • Cell Research
    Eon Kim 2 Jing Jing Lin 1 and Soo Young Lee 1 2 3 1 Division of Life and Pharmaceutical Sciences Ewha Womans University Seoul 120 750 Korea 2 Department of Bioinspired Science Ewha Womans University Seoul 120 750 Korea 3 Department of Life Science and the Research Center for Cellular Homeostasis Ewha Womans University Seoul 120 750 Korea Correspondence Soo Young Lee Tel 82 2 3277 3770 E mail leesy ewha ac kr The receptor activator of NF κB RANK and immunoreceptor tyrosine based activation motif ITAM containing adaptors are essential factors involved in regulating osteoclast formation and bone remodeling Here we identify early estrogen induced gene 1 EEIG1 as a novel RANK ligand RANKL inducible protein that physically interacts with RANK and further associates with Gab2 PLCγ2 and Tec Btk kinases upon RANKL stimulation EEIG1 positively regulates RANKL induced osteoclast formation likely due to its ability to facilitate RANKL stimulated PLCγ2 phosphorylation and NFATc1 induction In addition an inhibitory peptide designed to block RANK EEIG1 interaction inhibited RANKL induced bone destruction by reducing osteoclast formation Together our results identify EEIG1 as a novel RANK signaling component controlling RANK mediated osteoclast formation and suggest that targeting EEIG1 might represent

    Original URL path: http://www.cell-research.com/arts.asp?id=1646 (2016-02-14)
    Open archived version from archive

  • Cell Research
    Department of Chemistry Pittsburgh PA 15213 USA Correspondence Kausik Chakrabarti Bibo Li Tel 1 412 268 3123 1 216 687 2444 E mail kausik cmu edu libibo gmail com Telomerase is a ribonucleoprotein enzyme typically required for sustained cell proliferation Although both telomerase activity and the telomerase catalytic protein component TbTERT have been identified in the eukaryotic pathogen Trypanosoma brucei the RNA molecule that dictates telomere synthesis remains unknown Here we identify the RNA component of Trypanosoma brucei telomerase TbTR and provide phylogenetic and in vivo evidence for TbTR s native folding and activity We show that TbTR is processed through trans splicing and is a capped transcript that interacts and copurifies with TbTERT in vivo Deletion of TbTR caused progressive shortening of telomeres at a rate of 3 5 bp population doubling PD which can be rescued by ectopic expression of a wild type allele of TbTR in an apparent dose dependent manner Remarkably introduction of mutations in the TbTR template domain resulted in corresponding mutant telomere sequences demonstrating that telomere synthesis in T brucei is dependent on TbTR We also propose a secondary structure model for TbTR based on phylogenetic analysis and chemical probing experiments thus defining TbTR

    Original URL path: http://www.cell-research.com/arts.asp?id=1647 (2016-02-14)
    Open archived version from archive

  • Cell Research
    Wei Gu 1 1 Institute for Cancer Genetics and Department of Pathology and Cell Biology College of Physicians and Surgeons Columbia University 1130 St Nicholas Avenue New York NY 10032 USA Correspondence Wei Gu Tel 212 851 5282 E mail wg8 columbia edu The PTEN tumor suppressor is a lipid phosphatase that has a central role in regulating the phosphatidylinositol 3 kinase PI3K signal transduction cascade Nevertheless the mechanism by which the PTEN activity is regulated in cells needs further elucidation Although previous studies have shown that ubiquitination of PTEN can modulate its stability and subcellular localization the role of ubiquitination in the most critical aspect of PTEN function its phosphatase activity has not been fully addressed Here we identify a novel E3 ubiquitin ligase of PTEN Ret finger protein RFP that is able to promote atypical polyubiquitinations of PTEN These ubiquitinations do not lead to PTEN instability or relocalization but rather significantly inhibit PTEN phosphatase activity and therefore modulate its ability to regulate the PI3K signal transduction cascade Indeed RFP overexpression relieves PTEN mediated inhibitory effects on AKT activation in contrast RNAi mediated knockdown of endogenous RFP enhances the ability of PTEN to suppress AKT activation Moreover RFP mediated

    Original URL path: http://www.cell-research.com/arts.asp?id=1648 (2016-02-14)
    Open archived version from archive

  • Cell Research
    Lexington KY 40536 USA Correspondence Robert S Lahue Tel 353 91 49 5756 E mail bob lahue nuigalway ie Trinucleotide repeat expansions cause 17 heritable human neurological disorders In some diseases somatic expansions occur in non proliferating tissues such as brain where DNA replication is limited This finding stimulated significant interest in replication independent expansion mechanisms Aberrant DNA repair is a likely source based in part on mouse studies showing that somatic expansions are provoked by the DNA repair protein MutSβ Msh2 Msh3 complex Biochemical studies to date used cell free extracts or purified DNA repair proteins to yield partial reactions at triplet repeats The findings included expansions on one strand but not the other or processing of DNA hairpin structures thought to be important intermediates in the expansion process However it has been difficult to recapitulate complete expansions in vitro and the biochemical role of MutSβ remains controversial Here we use a novel in vitro assay to show that human cell free extracts catalyze expansions and contractions of trinucleotide repeats without the requirement for DNA replication The extract promotes a size range of expansions that is similar to certain diseases and triplet repeat length and sequence govern expansions in

    Original URL path: http://www.cell-research.com/arts.asp?id=1649 (2016-02-14)
    Open archived version from archive



  •