Reduced cell-substrate adhesion formation promotes cell migration in Dictyostelium

Many cells adhere to the extracellular matrix (ECM) for efficient cell migration. This adhesion is mediated by focal adhesions, a protein complex linking the ECM to the intracellular cytoskeleton. Focal adhesions have been studied extensively in metazoan mesenchymal cells, but recent research in physiological contexts and amoeboid cells suggests that focal adhesion regulation differs from the mesenchymal focal adhesion paradigm. Although focal adhesion machinery predates the origin of metazoans, focal adhesion formation and regulation during nonmetazoan cell migration is largely unexplored. We used Dictyostelium discoideum to investigate potential novel mechanisms and the evolution of focal adhesion regulation, as Dictyostelium are nonmetazoans that form cell-substrate adhesion structures for migration. We show that PaxillinB, the Dictyostelium homologue of Paxillin, localizes to dynamic cell-substrate adhesions. As expected, PaxillinB mutations decreased the number of cell-substrate adhesions. Unexpectedly, however, decreased cell-substrate adhesion number led to an increase in cell migration speed. These findings are in direct contrast to Paxillin function at focal adhesions and regulation of cell migration in mammalian cells, challenging the established focal adhesion model and providing insight into the evolution of cell-substrate adhesions and Paxillin function during cell migration.