Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes
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 phosphor...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/06156 |
| _version_ | 1811201181157949440 |
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| author | Roberto Villaseñor Hidenori Nonaka Perla Del Conte-Zerial Yannis Kalaidzidis Marino Zerial |
| author_facet | Roberto Villaseñor Hidenori Nonaka Perla Del Conte-Zerial Yannis Kalaidzidis Marino Zerial |
| author_sort | Roberto Villaseñor |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:17:43Z |
| format | Article |
| id | doaj.art-3b2f53c4f64b46b781d3bebd42a746f4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:17:43Z |
| publishDate | 2015-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3b2f53c4f64b46b781d3bebd42a746f42022-12-22T03:52:13ZengeLife Sciences Publications LtdeLife2050-084X2015-02-01410.7554/eLife.06156Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomesRoberto Villaseñor0Hidenori Nonaka1Perla Del Conte-Zerial2Yannis Kalaidzidis3Marino Zerial4Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, GermanyMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, GermanyMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, GermanyMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, RussiaMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, GermanyAn 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.https://elifesciences.org/articles/06156signal transductionendocytosismembrane transport |
| spellingShingle | Roberto Villaseñor Hidenori Nonaka Perla Del Conte-Zerial Yannis Kalaidzidis Marino Zerial Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes eLife signal transduction endocytosis membrane transport |
| title | Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes |
| title_full | Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes |
| title_fullStr | Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes |
| title_full_unstemmed | Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes |
| title_short | Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes |
| title_sort | regulation of egfr signal transduction by analogue to digital conversion in endosomes |
| topic | signal transduction endocytosis membrane transport |
| url | https://elifesciences.org/articles/06156 |
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