Organization of functional modules at cell adhesions. (A) Cell–ECM and cell–cell adhesions are compartmentalized in modules with distinct functional properties. Physical linkage between the actin cytoskeleton (gray) and transmembrane adhesion receptors (orange) is mediated by the actin linkage module (cyan), which contains actin-binding molecules. Regulation of this linkage and local actin organization is mediated by components of the actin regulatory (blue) and signaling (yellow) modules. (B) Molecular interactions of proteins in the different adhesion modules between the actin cytoskeleton (gray) and adhesion receptors (orange). Functional modules at both adhesion sites are spatially segregated (with partial overlap) and, in cell–ECM adhesions (left), are organized within vertical organizational strata between the plasma membrane and the actin cytoskeleton. Arp, Actin-related protein; ECM, extracellular matrix; EPLIN, “epithelial protein lost in neoplasm” (LIMA1); FAK, focal adhesion kinase; ILK, integrin-linked kinase; SFK, Src-family kinases.