Kindlins: essential regulators of integrin signalling and cell–matrix adhesion.

Integrin-mediated cell–ECM (extracellular matrix) adhesion is a fundamental process that controls cell behaviour. For correct cell–ECM adhesion, both the ligand-binding affinity and the spatial organization of integrins must be precisely controlled; how integrins are regulated, however, is not completely understood. Kindlins constitute a family of evolutionarily conserved cytoplasmic components of cell–ECM adhesions that bind to β-integrin cytoplasmic tails directly and cooperate with talin in integrin activation. In addition, kindlins interact with many components of cell–ECM adhesions—such as migfilin and integrin-linked kinase—to promote cytoskeletal reorganization. Loss of kindlins causes severe defects in integrin signalling, cell–ECM adhesion and cytoskeletal organization, resulting in early embryonic lethality (kindlin-2), postnatal lethality (kindlin-3) and Kindler syndrome (kindlin-1). It is therefore clear that kindlins, together with several other integrin-proximal proteins, are essential for integrin signalling and cell–ECM adhesion regulation. [ABSTRACT FROM AUTHOR]