Correlated receptor transport processes buffer single-cell heterogeneity

Research output: Contribution to journalArticle

Authors

  • Stefan M. Kallenberger
  • Feilim Mac Gabhann (Editor)
  • Anne L. Unger
  • Stefan Legewie
  • Konstantinos Lymperopoulos
  • Ursula Klingmüller
  • Roland Eils

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Article numbere1005779
Number of pages28
JournalPLoS Computational Biology
Volume13
Issue number9
Publication statusPublished - 25 Sep 2017