An in vivo phosphoregulation paradox for focal adhesions.

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.