FHOD1 Is Needed for Directed Forces and Adhesion Maturation during Cell Spreading and Migration

Matrix adhesions provide critical signals for cell growth or differentiation. They form through a number of distinct steps that follow integrin binding to matrix ligands. In an early step, integrins form clusters that support actin polymerization by an unknown mechanism. This raises the question of how actin polymerization occurs at the integrin clusters. We report here that a major formin in mouse fibroblasts, FHOD1, is recruited to integrin clusters, resulting in actin assembly. Using cell-spreading assays on lipid bilayers, solid substrates, and high-resolution force-sensing pillar arrays, we find that knockdown of FHOD1 impairs spreading, coordinated application of adhesive force, and adhesion maturation. Finally, we show that targeting of FHOD1 to the integrin sites depends on the direct interaction with Src family kinases and is upstream of the activation by Rho kinase. Thus, our findings provide insights into the mechanisms of cell migration with implications for development and disease.