An in vivo phosphoregulation paradox for focal adhesions

Abstract

Focal adhesions (FAs) dynamics regulate single cell migration. In this issue, Xue et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202206078) show that Y118 phosphorylation on Paxilin, a key FA protein, limits migration of cells in vivo. Unphosphorylated Paxilin is necessary for FA disassembly and cell motility. Their findings directly contradict results from in vitro experiments, emphasizing the need for recreating the in vivo complexity to understand how cells behave in their native environments.

Figure 1.

Working model for how Y118-Paxillin phosphorylation status regulates cell migration in the in vitro cell culture and in vivo conditions. Top: Under in vitro cell culture conditions, FAK phosphorylates Paxillin on Y118, leading to high levels of Y118-Paxillin phosphorylation in migrating cells. In migrating cells in vivo, FAK levels are low, and Y118-Paxillin lacks phosphorylation. Bottom: Expression of the non-phosphorylatable Y118F-Paxillin leads to reduced cell migration in vitro compared with cells expressing the Y118E-Paxillin phosphomimetic, likely through reduced focal adhesion disassembly rates and reduced CRKII-DOCK180/RacGEF recruitment to Paxillin-positive focal adhesions. However, in vivo, cells expressing the non-phosphorylatable Y118F-Paxillin exhibit increased cell migration, likely through increased focal adhesion disassembly rates, and increased recruitment of CRKII-DOCK180/RacGEF to Paxillin-positive focal adhesions. Figure and legend extracted from Xue et al. (4) with permission of the authors.