ZFIN ID: ZDB-PUB-191116-7
Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish
Coombs, C., Georgantzoglou, A., Walker, H.A., Patt, J., Merten, N., Poplimont, H., Busch-Nentwich, E.M., Williams, S., Kotsi, C., Kostenis, E., Sarris, M.
Date: 2019
Source: Nature communications   10: 5166 (Journal)
Registered Authors: Busch-Nentwich, Elisabeth, Sarris, Milka
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Cell Membrane/metabolism
  • Cell Movement
  • Down-Regulation
  • Endocytosis
  • Models, Biological
  • Mutagenesis/genetics
  • Mutation/genetics
  • Neutrophils/metabolism*
  • Protein Transport
  • Receptors, Interleukin-8A/chemistry
  • Receptors, Interleukin-8A/genetics
  • Receptors, Interleukin-8A/metabolism*
  • Receptors, Interleukin-8B/chemistry
  • Receptors, Interleukin-8B/genetics
  • Receptors, Interleukin-8B/metabolism*
  • Time Factors
  • Wounds and Injuries/pathology*
  • Zebrafish/metabolism*
PubMed: 31727891 Full text @ Nat. Commun.
Immune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.