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Systems survey of endocytosis by multiparametric image analysis.

MPG-Autoren
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Collinet,  Claudio
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Stöter,  Martin
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Bradshaw,  Charles R.
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Samusik,  Nikolay
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Rink,  Jochen
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Kenski,  Denise
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Habermann,  Bianca
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Buchholz,  Frank
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

Henschel,  Robert
Max Planck Society;

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Fava,  Eugenio
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Kalaidzidis,  Yannis
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Zerial,  Marino
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Zitation

Collinet, C., Stöter, M., Bradshaw, C. R., Samusik, N., Rink, J., Kenski, D., et al. (2010). Systems survey of endocytosis by multiparametric image analysis. Nature, 464(7286), 243-249.


Zitierlink: https://hdl.handle.net/21.11116/0000-0001-0C39-3
Zusammenfassung
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)-beta 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.