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PMID: 25650738 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes.

eLife ·Vol. 4 ·2015-02-04

Villaseñor R, Nonaka H, Del Conte-Zerial P, Kalaidzidis Y, Zerial M

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.

Keywords
cell biology endocytosis human membrane transport mouse rat signal transduction
MeSH Terms
Endosomes/metabolism ErbB Receptors/metabolism HeLa Cells Humans Microscopy, Confocal Protein Transport Signal Transduction
Chemicals
ErbB Receptors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Villaseñor Roberto
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Nonaka Hidenori
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Del Conte-Zerial Perla
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Kalaidzidis Yannis
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Zerial Marino
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
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Article Info
Journal
eLife
Abbr.
Elife
ISSN
2050-084X
DOI
10.7554/eLife.06156
Published
2015-02-04
Epub
2015-00-04
Language
English
Region
England
NLM ID
101579614
PMCID
PMC4384751
Subset
IM
External Links
PubMed source DOI: 10.7554/eLife.06156 PMC Full Text View journal details
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