Abstract:
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.
Projects: A1.3: Identification of crucial metabolic processes during hepatocyte pr..., A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., A3.5: The impact of cell polarity on metabolism detoxification and endoc..., C2: Organization of the sinusoidal system and the liver lobule - referen..., C5: Structural changes and functional consequences of the liver lobular/..., C6: Organization and function of the sinusoidal system and the liver lob...
Nature
Nature 464(7286): 243-9
28th Feb 2010
Claudio Collinet, Martin Stöter, 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
Authors
Attributions
None
Scales
Not Specified
- Created: 23rd Nov 2012 at 14:04
- Last updated: 24th Oct 2013 at 16:20
Related items
