PUBLICATION

Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Authors
Xue, Q., Varady, S.R.S., Waddell, T.Q.A., Roman, M.R., Carrington, J., Roh-Johnson, M.
ID
ZDB-PUB-230202-18
Date
2023
Source
The Journal of cell biology   222(3): (Journal)
Registered Authors
Roh-Johnson, Minna, Varady, Sophia, Waddell, Trinity, Xue, Qian
Keywords
none
MeSH Terms
  • Animals
  • Cell Movement*/physiology
  • Focal Adhesion Protein-Tyrosine Kinases/metabolism
  • Focal Adhesions*/metabolism
  • Mice
  • Paxillin*/genetics
  • Paxillin*/metabolism
  • Phosphorylation
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
36723624 Full text @ J. Cell Biol.
Abstract
Focal adhesions are structures that physically link the cell to the extracellular matrix for cell migration. Although cell culture studies have provided a wealth of information regarding focal adhesion biology, it is critical to understand how focal adhesions are dynamically regulated in their native environment. We developed a zebrafish system to visualize focal adhesion structures during single-cell migration in vivo. We find that a key site of phosphoregulation (Y118) on Paxillin exhibits reduced phosphorylation in migrating cells in vivo compared to in vitro. Furthermore, expression of a non-phosphorylatable version of Y118-Paxillin increases focal adhesion disassembly and promotes cell migration in vivo, despite inhibiting cell migration in vitro. Using a mouse model, we further find that the upstream kinase, focal adhesion kinase, is downregulated in cells in vivo, and cells expressing non-phosphorylatable Y118-Paxillin exhibit increased activation of the CRKII-DOCK180/RacGEF pathway. Our findings provide significant new insight into the intrinsic regulation of focal adhesions in cells migrating in their native environment.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping