Correlated receptor transport processes buffer single-cell heterogeneity

• Verfasst von: Kallenberger, Stefan M. [VerfasserIn]
• Verfasst von: Unger, Anne Lucia Katharina [VerfasserIn]
• Verfasst von: Klingmüller, Ursula [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Herten, Dirk-Peter [VerfasserIn]
• Titel: Correlated receptor transport processes buffer single-cell heterogeneity
• Verf.angabe: Stefan M. Kallenberger, Anne L. Unger, Stefan Legewie, Konstantinos Lymperopoulos, Ursula Klingmüller, Roland Eils, Dirk-Peter Herten
• E-Jahr: 2017
• Jahr: September 25, 2017
• Umfang: 14 S.
• Fussnoten: Gesehen am 19.04.2018
• Titel Quelle: Enthalten in: Public Library of SciencePLoS Computational Biology
• Ort Quelle: San Francisco, Calif. : Public Library of Science, 2005
• Jahr Quelle: 2017
• Band/Heft Quelle: 13(2017,9) Artikel-Nummer e1005779, 28 Seiten
• ISSN Quelle: 1553-7358
• DOI: doi:10.1371/journal.pcbi.1005779
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cell membranes
• Sach-SW: Hormone transport
• Sach-SW: Intracellular membranes
• Sach-SW: Intracellular receptors
• Sach-SW: Membrane receptor signaling
• Sach-SW: Membrane trafficking
• Sach-SW: Signal transduction
• Sach-SW: Vesicles
• K10plus-PPN: 1572172460
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

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.