PUBLICATION

Gβ1 is required for neutrophil migration in zebrafish

Authors
Ke, W., Ye, D., Mersch, K., Xu, H., Chen, S., Lin, F.
ID
ZDB-PUB-170531-10
Date
2017
Source
Developmental Biology   428(1): 135-147 (Journal)
Registered Authors
Lin, Fang, Xu, Hui, Ye, Ding
Keywords
Cell migration, G protein, Gβ1, imaging, neutrophil
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Chemotaxis, Leukocyte/physiology*
  • Class Ib Phosphatidylinositol 3-Kinase/metabolism
  • GTP-Binding Protein beta Subunits/antagonists & inhibitors
  • GTP-Binding Protein beta Subunits/genetics
  • GTP-Binding Protein beta Subunits/metabolism*
  • Heterotrimeric GTP-Binding Proteins/antagonists & inhibitors
  • Heterotrimeric GTP-Binding Proteins/genetics
  • Heterotrimeric GTP-Binding Proteins/metabolism*
  • Morpholinos/genetics
  • Neutrophils/physiology*
  • Signal Transduction
  • Wound Healing/physiology*
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
28554852 Full text @ Dev. Biol.
Abstract
Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes