The intermediate filament protein vimentin is involved in cell migration during wound healing and invasion, and localises to cell–matrix adhesion sites, where it interacts with focal-adhesion (FA) proteins, including integrin β1 and paxillin. However, it remains unclear how vimentin regulates cell migration through soft connective tissues, characterised by collagen matrices. In this study, Zofia Ostrowska-Podhorodecka and colleagues (Ostrowska-Podhorodecka et al., 2021) investigate whether vimentin might act as an adaptor to help orchestrate the efficient formation of cell adhesions to collagen. They show that depletion of vimentin in fibroblasts or mouse embryonic fibroblasts (MEFs) results in a twofold increase of integrin β1 activation, but integrin clustering was reduced by over 50%, in particular near the leading edge; this could be restored upon the re-expression of vimentin, suggesting a role in regulating integrin clustering and FA maturation. Vimentin-depleted cells also showed a reduced recruitment of paxillin to FAs, as well as a decrease in downstream Cdc42 activation. As demonstrated here, this impaired activation of PAK1, which is required for vimentin phosphorylation, which, in turn, promotes filament formation at FAs and their maturation. On the basis of these data, the authors propose that vimentin has a role of in fine-tuning cell adhesion by regulating integrin activation into functional and mature adhesions that allow for cell migration.
