Cell migration and invasion, which are fundamental to many cellular processes (for example, wound healing), require dynamic interactions between cells and the extracellular matrix (ECM) and the capacity of cells to degrade the ECM. Some highly motile and invasive cells form podosomes – dynamic actin-based structures that mediate cellular adhesion to the ECM and that promote localised degradation of the ECM to facilitate cell motility and invasion. Here (p. ), Anna Huttenlocher and co-workers investigate the regulation of podosome formation and cell invasion in Src-transformed fibroblasts by mammalian actin-binding protein 1 (mAbp1, also known as DBNL), an F-actin binding protein with high structural similarity to cortactin. The authors show that mAbp1 is required for the formation of podosome rosettes in Src-transformed cells, whereas cortactin is required for the formation of podosome dots. Furthermore, specific Src phosphorylation sites in mAbp1 mediate podosome rosette formation and ECM degradation. Unexpectedly, mAbp1-deficient cells are more invasive than cells expressing mAbp1 despite forming fewer rosettes, which suggests that mAbp1 differentially regulates ECM degradation and cell invasion. Together, these results identify a role for mAbp1 in podosome rosette formation and cell invasion downstream of Src.
