G?1 is required for neutrophil migration in zebrafish.

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 PI3K? 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 PI3K? is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit G?1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of G?? signaling, neutrophils failed to migrate to wound sites. Although both the G?1 and G?4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The G?1 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 PI3K?. Transplantation assays showed that the requirement for G?1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that G?1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that G?1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific G? isoform in chemotaxis in vivo.

SUBMITTER: Ke W 

PROVIDER: S-EPMC5799152 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature