title: Talins and kindlins: partners in integrin-mediated adhesion.
abstract: 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.
authors.affiliation: Departments of Pharmacology and of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. david.calderwood@ yale.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
authors.forename: Iain D
authors.initials: ID
authors.lastname: Campbell
authors.forename: David R
authors.initials: DR
authors.lastname: Critchley
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D005810:Multigene Family / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D016608:Talin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C475301:FERMT1 protein, human; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016608:Talin