Talins and kindlins: partners in integrin-mediated adhesion

The ability of integrins to link the extracellular environment to intracellular networks enables cells to respond to chemical and physical cues. Insight has been gained into how talins and kindlins, two families of FERM-domain proteins that bind the cytoplasmic tail of integrins, mediate integrin activation and the cellular processes that depend on this. Integrin receptors provide a dynamic, tightly-regulated link between the extracellular matrix (or cellular counter-receptors) and intracellular cytoskeletal and signalling networks, enabling cells to sense and respond to their chemical and physical environment. Talins and kindlins, two families of FERM–domain proteins, bind the cytoplasmic tail of integrins, recruit cytoskeletal and signalling proteins involved in mechanotransduction and synergize to activate integrin binding to extracellular ligands. New data reveal the domain structure of full-length talin, provide insights into talin-mediated integrin activation and show that RIAM recruits talin to the plasma membrane, whereas vinculin stabilizes talin in cell–matrix junctions. How kindlins act is less well-defined, but disease-causing mutations show that kindlins are also essential for integrin activation, adhesion, cell spreading and signalling.