Dynamic Buffering of Extracellular Chemokine by a Dedicated Scavenger Pathway Enables Robust Adaptation during Directed Tissue Migration.

Autor:	Wong M; Department of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany. Electronic address: mie.wong@uzh.ch., Newton LR; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Hartmann J; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Hennrich ML; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Wachsmuth M; Luxendo GmbH, Kurfürsten-Anlage 58, 69115 Heidelberg, Germany., Ronchi P; Electron Microscopy Core Facility, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Guzmán-Herrera A; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Schwab Y; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany; Electron Microscopy Core Facility, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany., Gavin AC; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany; Department for Cell Physiology and Metabolism, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland., Gilmour D; Department of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany. Electronic address: darren.gilmour@uzh.ch.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2020 Feb 24; Vol. 52 (4), pp. 492-508.e10. Date of Electronic Publication: 2020 Feb 13.
DOI:	10.1016/j.devcel.2020.01.013
Abstrakt:	How tissues migrate robustly through changing guidance landscapes is poorly understood. Here, quantitative imaging is combined with inducible perturbation experiments to investigate the mechanisms that ensure robust tissue migration in vivo. We show that tissues exposed to acute "chemokine floods" halt transiently before they perfectly adapt, i.e., return to the baseline migration behavior in the continued presence of elevated chemokine levels. A chemokine-triggered phosphorylation of the atypical chemokine receptor Cxcr7b reroutes it from constitutive ubiquitination-regulated degradation to plasma membrane recycling, thus coupling scavenging capacity to extracellular chemokine levels. Finally, tissues expressing phosphorylation-deficient Cxcr7b migrate normally in the presence of physiological chemokine levels but show delayed recovery when challenged with elevated chemokine concentrations. This work establishes that adaptation to chemokine fluctuations can be "outsourced" from canonical GPCR signaling to an autonomously acting scavenger receptor that both senses and dynamically buffers chemokine levels to increase the robustness of tissue migration. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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