Lack of Paxillin phosphorylation promotes single-cell migration in vivo.
Qian XueSophia R S VaradyTrinity Q Alaka'i WaddellMackenzie R RomanJames CarringtonMinna Roh-JohnsonPublished in: The Journal of cell biology (2023)
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.
Keyphrases
- cell migration
- induced apoptosis
- cell cycle arrest
- mouse model
- extracellular matrix
- signaling pathway
- endoplasmic reticulum stress
- stem cells
- healthcare
- oxidative stress
- single cell
- high resolution
- cell proliferation
- transcription factor
- cell therapy
- pseudomonas aeruginosa
- bone marrow
- mesenchymal stem cells
- social media
- cystic fibrosis
- wild type
- cell adhesion