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Systems survey of endocytosis by multiparametric image analysis

机译：通过多参数图像分析对内吞作用进行系统调查

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摘要

Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-p and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.
机译：胞吞作用是完成许多细胞和发育功能的复杂过程。了解它是如何调节和与其他细胞过程整合的，需要对其分子组成和一般设计原理进行全面分析。在这里，我们开发了一种新的策略，通过结合RNA干扰，自动高分辨率共聚焦显微镜，定量多参数图像分析和高性能计算，就转铁蛋白（TF）和表皮生长因子（EGF）内吞作用对人类基因组进行了表型分析。我们确定了内吞运输的几个新的组成部分，包括与人类疾病有关的基因。我们发现诸如Wnt，整联蛋白/细胞粘附，转化生长因子（TGF）-p和Notch的信号通路调节内吞系统，并鉴定了参与货物分选的新基因，成为信号内体的一个子集。通过贝叶斯网络进行的系统分析进一步表明，内体的数量，大小，货物浓度和胞内位置不是随机确定的，而是受到特定调节的，从而揭示了内吞系统的新特性。

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  • 来源
    《Nature》 |2010年第7286期|243-249|共7页
  • 作者

    Ciaudio Collinet; Martin Stoeter; Charles R. Bradshaw; Nikolay Samusik; Jochen C. Rink; Denise Kenski; Bianca Habermann; Frank Buchholz; Robert Henschel; Matthias S. Mueller; Wolfgang E. Nagel; Eugenio Fava; Yannis Kalaidzidis; Marino Zerial;

  • 作者单位

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    High-Throughput Technology Development Studio, MPI-CBG, Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    University of Utah School of Medicine, 401 MREB, 20 North 1900 East, Salt Lake City. Utah 84132-3401, USA;

    Sirna Therapeutics Inc., San Francisco, California 94158, USA;

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    Center for Information Services and High Performance Computing (ZIH), Dresden University of Technology, D-01062 Dresden, Germany;

    Center for Information Services and High Performance Computing (ZIH), Dresden University of Technology, D-01062 Dresden, Germany;

    Center for Information Services and High Performance Computing (ZIH), Dresden University of Technology, D-01062 Dresden, Germany;

    High-Throughput Technology Development Studio, MPI-CBG, Pfotenhauerstrasse 108, 01307 Dresden, Germany;

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119899, Moscow, Russia;

    Max Planck Institute for Molecular Cell Biology and Genetics Pfotenhauerstrasse 108, 01307 Dresden, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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