Wound healing in epithelial cells is mediated by reorganisation of the cytoskeleton and of cell–matrix adhesions, including focal adhesions (FAs), and is coordinated by small GTPases and their regulators. One of these is the guanine nucleotide exchange factor (GEF) β-PIX; this protein has been shown to be a negative regulator of FA maturation and to activate Rac1 and Rho. In this work (p. 2329), Jonathan Jones and colleagues now assess the role of β-PIX in the motility of single keratinocytes and in the collective cell migration of groups of these cells. Surprisingly, knockdown of β-PIX in keratinocytes results in an increase in their motility, both in single cells and for cells in a wounded monolayer. This might be explained by the larger FAs keratinocytes exhibit in the absence of β-PIX and the increase in traction forces observed. With regard to the underlying mechanism, the authors show that upon knockdown of β-PIX, the distribution of phosphorylated myosin light chain (MLC) is altered and p21-activated kinase 2 (PAK2), which regulates MLC kinase (MYLK), is mislocalised. Accordingly, inhibition or depletion of MYLK in these cells restored normal FA size and reduced their motility. Taken together, these findings point to the possibility that decreasing β-PIX expression or inhibiting its function locally at a wound site could help to accelerate wound healing in an in vivo setting.
