Figure 5
From: Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation
Talin changes binding partners in response to force induced conformational change.
Force plays a key role in driving the formation of FA. 0–5 pN: RIAM recruits autoinhibited talin to the plasma membrane in a Rap1.GTP dependent manner via synergistic binding of RIAM to the R2–R3 domains of talin. At the membrane talin autoinhibition is relieved by interactions with acidic membrane phospholipids. Talin can then activate integrins. ∼5 pN: Only when talin has engaged the integrins and also captured the retrograde flow of actin is force exerted on talin. At ∼5 pN, the force of a single actomyosin contraction, the R3 domain is destabilized and this reduces RIAM binding whilst exposing the high affinity VBS which then bind vinculin strengthening the adhesion. >5 pN: With more vinculin cross-linking the adhesion can withstand greater force exposing further VBS. >25 pN: At sufficiently high forces vinculin is displaced, resulting in unfolding of the VBS to a random coil.
