Fig 5. Crosstalk between talin and kindlin in displacement model of integrin activation.

(1) In the first step, filamin bound to resting integrins can be displaced from β CT by migfilin, possibly recruited by kindlins to the vicinity of integrin tails. (2) This makes integrin β CT available for binding by talin at the proximal NPxY/F motif, which unclasps the integrins. 3) Kindlin binding converts the early stage of activated integrin to a high affinity state, allowing ligand binding. 4) Cooperative talin and kindlin binding to β CT may lead to crosstalk between integrins leading to clustered integrins and outside-in-signaling. It is still not clear if migfilin remains associated with kindlin after kindlin-β CT engagement and what are the events that trigger dissociation of migfilin-filamin contacts during this process.