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 beta-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.
Larjava
Hannu
H
Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
Plow
Edward F
EF
Wu
Chuanyue
C
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D021982:Cell-Matrix Junctions / Q000378:metabolism*; D004194:Disease; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D015398:Signal Transduction
D002352:Carrier Proteins; D016023:Integrins