Dynamic buffering of extracellular chemokine by a dedicated scavenger pathway enables robust adaptation during directed tissue migration
| Autor: | Anne-Claude Gavin, Malte Wachsmuth, Alejandra Guzmán-Herrera, Yannick Schwab, Mie Wong, Jonas Hartmann, Paolo Ronchi, Darren Gilmour, Lionel R. Newton, Marco L. Hennrich |
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| Přispěvatelé: | University of Zurich, Wong, Mie |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Chemokine
Receptors CXCR4 Embryo Nonmammalian Cell Communication General Biochemistry Genetics and Molecular Biology 1309 Developmental Biology 1307 Cell Biology 03 medical and health sciences Chemokine receptor 0302 clinical medicine Cell Movement 1300 General Biochemistry Genetics and Molecular Biology Extracellular 1312 Molecular Biology Animals Scavenger receptor Phosphorylation ddc:612 Molecular Biology Zebrafish 030304 developmental biology G protein-coupled receptor Receptors CXCR 0303 health sciences biology Tissue migration Cell migration Cell Biology Zebrafish Proteins 10124 Institute of Molecular Life Sciences Cell biology biology.protein 570 Life sciences Chemokines 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Developmental Cell, Vol. 52, No 4 (2020) pp. 492-508.e10 |
| ISSN: | 1534-5807 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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