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Progress and perspective of cellular dynamics studies

  • School of Life Science, University of Science and Technology of China, Hefei 230027, China

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  • Received Date: 28 June 2008
  • Rev Recd Date: 28 July 2008
  • Publish Date: 31 August 2008
    Abstract

  • Abstract

    The cell is a fundamental building block of life. Cellular dynamics and plasticity are essential for animal development, growth and reproduction. At the molecular level, cellular plasticity and dynamics are governed by genetic and epigenetic regulations. With the completion of animal genomes and elucidation biochemical characterization of macromolecule interactions, it is becoming increasingly important to delineate the spatiotemporal dynamics and regulation of key regulators underlying cellular dynamics such as cell division, which was the chief objective to build the Laboratory of Cellular Dynamics in the University of Science and Technology of China at the beginning of this Millennium. Using kinetochore assembly in mitosis as a model system, the Laboratory of Cellular Dynamics has successfully carried out molecular dissection of mammalian kinetochore composition, elucidated several important kinetochore interacting networks and illustrated the key regulator dynamics. Toward the completion of molecular delineation of mammalian kinetochore interactome and signaling cascades, the Lab aims to illuminate the molecular dynamics underlying kinetochore assembly at nano-scale. Successful accomplishment of their long-term objectives will enable us to consolidate dynamic protein-protein interactome into nano-scale physiology, which will provide a launch-pad for solving complex biological questions such as stem cell plasticity and for designing better anti-cancer drugs.

    Abstract

    The cell is a fundamental building block of life. Cellular dynamics and plasticity are essential for animal development, growth and reproduction. At the molecular level, cellular plasticity and dynamics are governed by genetic and epigenetic regulations. With the completion of animal genomes and elucidation biochemical characterization of macromolecule interactions, it is becoming increasingly important to delineate the spatiotemporal dynamics and regulation of key regulators underlying cellular dynamics such as cell division, which was the chief objective to build the Laboratory of Cellular Dynamics in the University of Science and Technology of China at the beginning of this Millennium. Using kinetochore assembly in mitosis as a model system, the Laboratory of Cellular Dynamics has successfully carried out molecular dissection of mammalian kinetochore composition, elucidated several important kinetochore interacting networks and illustrated the key regulator dynamics. Toward the completion of molecular delineation of mammalian kinetochore interactome and signaling cascades, the Lab aims to illuminate the molecular dynamics underlying kinetochore assembly at nano-scale. Successful accomplishment of their long-term objectives will enable us to consolidate dynamic protein-protein interactome into nano-scale physiology, which will provide a launch-pad for solving complex biological questions such as stem cell plasticity and for designing better anti-cancer drugs.
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    • References(27)
  • [1]
    姚健晖, 郑宇鹏, 姚雪彪. 纺锤体检验点的功能与染色体不稳定性[J].科学通报，2002，47（2）：81-87.
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    Du J, Cai X, Yao J, et al. The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability[J]. Oncogene,2008, 27:4 107-4 114.
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    Yao X, Zheng Y, Sullivan K F, et al. CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint[J]. Nature Cell Biology,2000,2:484-491.
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    Yao X, Anderson K L, Cleveland D W. The microtubule-dependent motor centromere-associated protein E (CENP-E) an integral component of kinetochore corona fibers that link centromeres to spindle microtubules[J]. J Cell Biol,1997,139:435-447.
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    [22]
    Liu D, Ge L, Wang F, et al. Single-molecule detection of phosphorylation-induced plasticity changes during ezrin activation[J]. FEBS Lett, 2007,581(18):3 563-3 571.
    [23]
    Wang F, Xia P, Wu F, et al. Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells[J]. Journal of Biological Chemistry, 2008，doi: 10.1074/jbc.M80057200.
    [24]
    Fang Z, Miao Y, Ding X, et al. Proteomic identification and functional characterization of a novel ARF6 GTPase-activating protein ACAP4[J]. Mol & Cell Proteomics,2006,5:1 437-1 449.
    [25]
    Betzig E, et al. Imaging intracellular fluorescent proteins at nanometer resolution[J]. Science, 2006,313:1 642-1 645.
    [26]
    Huang B, Wang W, Bates M, et al. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy[J]. Science, 2008,319:810-813.
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    Bates M, Wang B, Dumpsey G P T, et al. Multicolor super-resolution imaging with photo-switchable fluorescent probes[J]. Science, 2007,317:1 749-1 753.
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    [1]
    姚健晖, 郑宇鹏, 姚雪彪. 纺锤体检验点的功能与染色体不稳定性[J].科学通报，2002，47（2）：81-87.
    [2]
    Lou Y, Yao J, Zereshki A, et al. NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling[J]. Journal of Biological Chemistry,2004,279:20 049-20 057.
    [3]
    Yao J, Fu C, Ding X, et al. Nek2A kinase regulates the localization of numatrin to centrosome in mitosis[J]. FEBS Letters,2004, 575: 112-118.
    [4]
    Fu G, Ding X, Yuan K, et al. Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis[J]. Cell Res, 2007,17(7):608-618.
    [5]
    Du J, Cai X, Yao J, et al. The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability[J]. Oncogene,2008, 27:4 107-4 114.
    [6]
    Ke Y, Dou Z, Zhang J, et al. Function and regulation of Aurora/Ipl1p kinase family in cell division[J]. Cell Res,2003,13: 69-81.
    [7]
    Yang Y, Wu F, Ward T, et al. Phosphorylation of HsMis13 by aurora B is essential for assembly of functional kinetochore[J]. Journal of Biological Chemistry, 2008, doi: 10.1074/jbc.M804207200.
    [8]
    Xue Y, Zhou F, Lu H, et al. GPS: a comprehensive www server for phosphorylation sites prediction[J]. Nucleic Acids Research,2005, 33:W184-187.
    [9]
    Zhou F, Xue Y, Yao X, et al. A general user interface for prediction servers of proteins post-translational modification sites[J]. Nature Protocol, 2006,1(3):1 318-1 321.
    [10]
    Xue Y, Ren J, Gao X, et al. GPS 20: Prediction of kinase-specific phosphorylation sites in hierarchy[J]. Mol Cell Proteomics,2008,doi: 10.1074/mcp.M700574-MCP200/18463090.
    [11]
    Zhang J, Dou Z, Miao Y, et al. TTK is a kinetochore-associated spindle checkpoint kinase and co-localized with CENP-E[J]. Science Bulletin,2002, 27:213-219.
    [12]
    Dou Z, Sawagechi A, Zhang J, et al. Dynamic distribution of TTK in HeLa cells: insights from an ultrastructural study[J]. Cell Research, 2003,13: 443-449.
    [13]
    Dou Z, Ding X, Zereshki A, et al. TTK kinase is essential for the centrosomal localization of TACC2[J]. FEBS Letters, 2004,572:51-56.
    [14]
    Yao X, Zheng Y, Sullivan K F, et al. CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint[J]. Nature Cell Biology,2000,2:484-491.
    [15]
    Yao X, Anderson K L, Cleveland D W. The microtubule-dependent motor centromere-associated protein E (CENP-E) an integral component of kinetochore corona fibers that link centromeres to spindle microtubules[J]. J Cell Biol,1997,139:435-447.
    [16]
    Zhu M, Wang F, Yan F, et al. Septin 7 interacts with centromere-associated protein E and is required for its kinetochore localization[J]. Journal of Biological Chemistry, 2008,283(27):18 916-18 925.
    [17]
    Liu D, Ding X, Du J, et al. Human NUF2 interacts with centromere-associated protein E and is essential for a stable spindle microtubule-kinetochore attachment[J]. Journal of Biological Chemistry, 2007,282(29):21 415-21 424.
    [18]
    Wang H, Hu X, Ding X, et al. Human Zwint-1 specifies localization of Zeste White 10 to kinetochores and is essential for mitotic checkpoint signaling[J]. Journal of Biological Chemistry,2004,279: 54 590-54 598.
    [19]
    Yao X, Forte J G. Cell biology of acid secretion by parietal cells[J]. Ann Rev Physiol, 2003,65:103-131.
    [20]
    Zhou R, Cao X, Watson C, et al. Characterization of protein kinase A-mediated phosphorylation of ezrin in gastric parietal cell activation[J]. Journal of Biological Chemistry, 2003,278: 35 651-35 659.
    [21]
    Cao X, Ding X, Guo Z, et al. PALS1 specifies the localization of ezrin to the apical membrane of gastric parietal cells[J]. Journal of Biological Chemistry, 2005,280: 13 584-13 592.
    [22]
    Liu D, Ge L, Wang F, et al. Single-molecule detection of phosphorylation-induced plasticity changes during ezrin activation[J]. FEBS Lett, 2007,581(18):3 563-3 571.
    [23]
    Wang F, Xia P, Wu F, et al. Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells[J]. Journal of Biological Chemistry, 2008，doi: 10.1074/jbc.M80057200.
    [24]
    Fang Z, Miao Y, Ding X, et al. Proteomic identification and functional characterization of a novel ARF6 GTPase-activating protein ACAP4[J]. Mol & Cell Proteomics,2006,5:1 437-1 449.
    [25]
    Betzig E, et al. Imaging intracellular fluorescent proteins at nanometer resolution[J]. Science, 2006,313:1 642-1 645.
    [26]
    Huang B, Wang W, Bates M, et al. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy[J]. Science, 2008,319:810-813.
    [27]
    Bates M, Wang B, Dumpsey G P T, et al. Multicolor super-resolution imaging with photo-switchable fluorescent probes[J]. Science, 2007,317:1 749-1 753.
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