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

• DOI: 10.1016/j.devcel.2020.01.013
• Publication Date: 2020-02-13T15:33:27Z
• Authors: Mie Wong; Lionel R. Newton; Jonas Hartmann; Marco L. Hennrich; Malte Wachsmuth; Paolo Ronchi; Alejandra Guzmán-...; Yannick Schwab; Anne-Claude Gavin; Darren Gilmour
• Keywords: Receptors, CXCR; Receptors, CXCR4; 0303 health sciences; Embryo, Nonmammalian; Cell Communication; Zebrafish Proteins; 10124 Institute of Molecular Life Sciences; 1309 Developmental Biology; 1307 Cell Biology; 03 medical and health sciences; 1300 General Biochemistry, Genetics and Molecular Biology; Cell Movement; 1312 Molecular Biology; 570 Life sciences; biology; Animals; info:eu-repo/classification/ddc/612; Chemokines; Phosphorylation; ddc:612; Zebrafish; Signal Transduction

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.