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Correlated receptor transport processes buffer single-cell heterogeneity

Cells typically vary in their response to extracellular ligands. Receptor transport processes modulate ligand-receptor induced signal transduction and impact the variability in cellular responses. Here, we quantitatively characterized cellular variability in erythropoietin receptor (EpoR) traffickin...

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Bibliographic Details
Main Authors: Kallenberger, Stefan M. (Author) , Unger, Anne Lucia Katharina (Author) , Klingmüller, Ursula (Author) , Eils, Roland (Author) , Herten, Dirk-Peter (Author)
Format: Article (Journal)
Language:English
Published: September 25, 2017
In: PLoS Computational Biology
Year: 2017, Volume: 13, Issue: 9
ISSN:1553-7358
DOI:10.1371/journal.pcbi.1005779
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pcbi.1005779
Verlag, kostenfrei, Volltext: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005779
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Author Notes:Stefan M. Kallenberger, Anne L. Unger, Stefan Legewie, Konstantinos Lymperopoulos, Ursula Klingmüller, Roland Eils, Dirk-Peter Herten
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Summary:Cells typically vary in their response to extracellular ligands. Receptor transport processes modulate ligand-receptor induced signal transduction and impact the variability in cellular responses. Here, we quantitatively characterized cellular variability in erythropoietin receptor (EpoR) trafficking at the single-cell level based on live-cell imaging and mathematical modeling. Using ensembles of single-cell mathematical models reduced parameter uncertainties and showed that rapid EpoR turnover, transport of internalized EpoR back to the plasma membrane, and degradation of Epo-EpoR complexes were essential for receptor trafficking. EpoR trafficking dynamics in adherent H838 lung cancer cells closely resembled the dynamics previously characterized by mathematical modeling in suspension cells, indicating that dynamic properties of the EpoR system are widely conserved. Receptor transport processes differed by one order of magnitude between individual cells. However, the concentration of activated Epo-EpoR complexes was less variable due to the correlated kinetics of opposing transport processes acting as a buffering system.
Item Description:Gesehen am 19.04.2018
Physical Description:Online Resource
ISSN:1553-7358
DOI:10.1371/journal.pcbi.1005779

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