title: Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes.
abstract: An outstanding question is how receptor tyrosine kinases (RTKs) determine different cell-fate decisions despite sharing the same signalling cascades. Here, we uncovered an unexpected mechanism of RTK trafficking in this process. By quantitative high-resolution FRET microscopy, we found that phosphorylated epidermal growth factor receptor (p-EGFR) is not randomly distributed but packaged at constant mean amounts in endosomes. Cells respond to higher EGF concentrations by increasing the number of endosomes but keeping the mean p-EGFR content per endosome almost constant. By mathematical modelling, we found that this mechanism confers both robustness and regulation to signalling output. Different growth factors caused specific changes in endosome number and size in various cell systems and changing the distribution of p-EGFR between endosomes was sufficient to reprogram cell-fate decision upon EGF stimulation. We propose that the packaging of p-RTKs in endosomes is a general mechanism to ensure the fidelity and specificity of the signalling response.
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors: Roberto
authors: R
authors: Villaseñor
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors: Hidenori
authors: H
authors: Nonaka
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors: Perla
authors: P
authors: Del Conte-Zerial
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors: Yannis
authors: Y
authors: Kalaidzidis
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors: Marino
authors: M
authors: Zerial
mesh_terms: D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D066246:ErbB Receptors
keywords: cell biology; endocytosis; human; membrane transport; mouse; rat; signal transduction
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