Make and break: the vinculin-lipid connection

The turnover of small transient cell-matrix adhesion sites, which is required for cell spreading and migration, is thought to depend on local phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P₂] concentrations. Previous studies have suggested that the binding of PtdIns(4,5)P₂ to vinculin, a structural component of adhesion sites, promotes vinculin's activation and targeting to adhesion sites, where it binds talin and actin. On p. 1461, Wolfgang Ziegler and colleagues challenge this idea, showing that it is adhesion-site turnover rather than vinculin targeting that depends on the PtdIns(4,5)P₂-vinculin interaction. The authors have constructed vinculin-LD, a vinculin mutant lacking PtdIns(4,5)P₂-binding sites, and expressed it in a mouse melanoma cell line. Vinculin-LD is readily recruited to adhesion sites but adhesion-site turnover is reduced, resulting in impaired cell spreading and migration. Furthermore, vinculin-LD expression suppresses the disassembly of adhesion sites and cell detachment usually seen when PtdIns(4,5)P₂ levels are increased by overexpression of PIP 5-kinase. Vinculin, the authors conclude, is a sensor that converts local modulation of PtdIns(4,5)P₂ levels into adhesion-site dynamics.