Journal article
Gβ1 is required for neutrophil migration in zebrafish
Developmental biology, Vol.428(1), pp.135-147
08/01/2017
DOI: 10.1016/j.ydbio.2017.05.024
PMCID: PMC5799152
PMID: 28554852
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.
•Gβγ signaling is required for the general motility and directed migration of neutrophils.•The requirement for Gβ1 in the directed migration of neutrophils is cell autonomous.•Gβ1 is required for the polarized activation of PI3K and actin dynamics.
Details
- Title: Subtitle
- Gβ1 is required for neutrophil migration in zebrafish
- Creators
- Wenfan Ke - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USADing Ye - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USAKacey Mersch - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USAHui Xu - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USASonghai Chen - Department of Pharmacology, Carver College of Medicine, University of Iowa, USAFang Lin - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Developmental biology, Vol.428(1), pp.135-147
- DOI
- 10.1016/j.ydbio.2017.05.024
- PMID
- 28554852
- PMCID
- PMC5799152
- NLM abbreviation
- Dev Biol
- ISSN
- 0012-1606
- eISSN
- 1095-564X
- Publisher
- Elsevier Inc
- Grant note
- name: NIH/NCRR, award: K99R00RR024119; DOI: 10.13039/100000001, name: National Science Foundation, award: IOS-1354457, AHA10GRNT3620015; DOI: 10.13039/100000002, name: NIH, award: R01GM094255
- Language
- English
- Date published
- 08/01/2017
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984025374602771
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