PUBLICATION
Dynamic Buffering of Extracellular Chemokine by a Dedicated Scavenger Pathway Enables Robust Adaptation during Directed Tissue Migration
- Authors
- Wong, M., Newton, L.R., Hartmann, J., Hennrich, M.L., Wachsmuth, M., Ronchi, P., Guzmán-Herrera, A., Schwab, Y., Gavin, A.C., Gilmour, D.
- ID
- ZDB-PUB-200216-10
- Date
- 2020
- Source
- Developmental Cell 52(4): 492-508.e10 (Journal)
- Registered Authors
- Gilmour, Darren
- Keywords
- GPCR, adaptation, cell migration, chemokine, live imaging, membrane trafficking, robustness, self-generated gradients, zebrafish
- MeSH Terms
-
- Animals
- Cell Communication
- Cell Movement*
- Chemokines/genetics
- Chemokines/metabolism*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism*
- Phosphorylation
- Receptors, CXCR/genetics
- Receptors, CXCR/metabolism*
- Receptors, CXCR4/genetics
- Receptors, CXCR4/metabolism*
- Signal Transduction
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32059773 Full text @ Dev. Cell
Citation
Wong, M., Newton, L.R., Hartmann, J., Hennrich, M.L., Wachsmuth, M., Ronchi, P., Guzmán-Herrera, A., Schwab, Y., Gavin, A.C., Gilmour, D. (2020) Dynamic Buffering of Extracellular Chemokine by a Dedicated Scavenger Pathway Enables Robust Adaptation during Directed Tissue Migration. Developmental Cell. 52(4):492-508.e10.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping