Article

Nature 464, 243-249 (11 March 2010) | doi:10.1038/nature08779; Received 1 December 2008; Accepted 17 December 2009; Published online 28 February 2010; Corrected 11 March 2009

There is a Corrigendum (18 September 2014) associated with this document.

Systems survey of endocytosis by multiparametric image analysis

Claudio Collinet1, Martin Stöter2, Charles R. Bradshaw1, Nikolay Samusik1, Jochen C. Rink5, Denise Kenski5, Bianca Habermann1, Frank Buchholz1, Robert Henschel3, Matthias S. Mueller3, Wolfgang E. Nagel3, Eugenio Fava2, Yannis Kalaidzidis1,4 & Marino Zerial1

  1. Max Planck Institute for Molecular Cell Biology and Genetics,
  2. High-Throughput Technology Development Studio, MPI-CBG, Pfotenhauerstrasse 108, 01307 Dresden, Germany
  3. Center for Information Services and High Performance Computing (ZIH), Dresden University of Technology, D-01062 Dresden, Germany
  4. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119899, Moscow, Russia
  5. Present addresses: University of Utah School of Medicine, 401 MREB, 20 North 1900 East, Salt Lake City, Utah 84132-3401, USA (J.C.R.); Sirna Therapeutics Inc., San Francisco, California 94158, USA (D.K.).

Correspondence to: Marino Zerial1 Correspondence and requests for materials should be addressed to M.Z. (Email: zerial@mpi-cbg.de).

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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)-β 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.

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