Lack of Paxillin phosphorylation promotes single-cell migration in vivo.

Qian Xue, Sophia R S Varady, Trinity Q Alaka'i Waddell, Mackenzie R Roman, James Carrington, Minna Roh-Johnson

The Journal of cell biology 2023 Mar 06

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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. © 2023 Xue et al.

Citation

Qian Xue, Sophia R S Varady, Trinity Q Alaka'i Waddell, Mackenzie R Roman, James Carrington, Minna Roh-Johnson. Lack of Paxillin phosphorylation promotes single-cell migration in vivo. The Journal of cell biology. 2023 Mar 06;222(3)