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

Area of Science:

• Cell migration
• Developmental biology
• Chemotaxis

Background:

• Robust tissue migration through dynamic environments is crucial for development and disease.
• Understanding how cells adapt to fluctuating guidance cues remains a challenge.

Purpose of the Study:

• To investigate the mechanisms underlying robust tissue migration in response to changing chemokine landscapes.
• To elucidate the role of atypical chemokine receptor Cxcr7b in adaptation to chemokine gradients.

Main Methods:

• Quantitative imaging and inducible perturbation experiments in vivo.
• Analysis of Cxcr7b phosphorylation, degradation, and recycling pathways.
• Assessment of tissue migration in response to acute chemokine level changes.

Main Results:

• Tissues exhibit transient halts and adaptation to acute "chemokine floods."
• Chemokine-triggered Cxcr7b phosphorylation redirects it from degradation to recycling.
• Phosphorylation-deficient Cxcr7b impairs adaptation to elevated chemokine levels.

Conclusions:

• Cxcr7b acts as an autonomous scavenger receptor, sensing and buffering chemokine levels.
• Adaptation to chemokine fluctuations is achieved by Cxcr7b, enhancing migration robustness.
• This mechanism decouples adaptation from canonical G protein-coupled receptor signaling.