Lack of Paxillin phosphorylation promotes single-cell migration in vivo

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. Xue et al. develop a system to visualize and compare focal adhesion formation and dynamics during single-cell migration in animal models versus cell culture systems. They reveal fundamental differences in the regulation of key focal adhesion proteins.

Automated summary

This study reveals the dynamic regulation of focal adhesions in cell migration in the native environment using a zebrafish model and a mouse model. The researchers found that the phosphorylation of Y118-Paxillin, a key site of phosphoregulation, is reduced in migrating cells in vivo compared to in vitro. Furthermore, expression of a non-phosphorylatable version of Y118-Paxillin promotes focal adhesion disassembly and cell migration in vivo. The findings also suggest that the CRKII-DOCK180/RacGEF pathway is activated in cells expressing non-phosphorylatable Y118-Paxillin.