Alternative splicing of exon 20 removes 2.4 helices from the Vt five-helix bundomainmain, deleting the actin interaction sites as well as essential parts of the head interaction sites and promotes constitutive ligand binding of the vinculin head.
Moreover, it is also possible that the binding of the vinculin head domain to talin may further activate the integrin receptors and increase its ligand binding affinity, although such a mechanism has not yet been demonstrated.
This suggests that binding of integrin, vinculin, or another molecule is critical, although the existence of many other VBSs in this truncation argues against it being vinculin.
The interaction with talin, the main regulator of integrin activation [ 19], is essential for the role of vinculin in FA stabilization [ 20], whereas binding of vinculin to F-actin contributes to the ability of the cell to exert tensile forces on the extracellular matrix (ECM).
The binding of vinculin to VASP is mediated by the first proline-rich region in the vinculin neck domain (Brindle et al., 1996).
Force-independent binding of Vinculin to α-catenin-1-402 α-catenin-1-402 α-catenin-1-402 α-catenin-1-402ura et al., 2010).
Recent reports indicate that while RIAM recruits talin to nascent adhesions, binding of vinculin to talin then displaces RIAM, stabilizing active integrins within focal adhesions (FAs).
Under these conditions, the direct binding of vinculin to talin and actin enables an efficient transfer of mechanical cues from the outer environment to the inside of the cell, thus permitting cells to react to changing mechanical stimuli.
43 By exposing the buried VBS in talin R1 R3 forces in the 5 30 pN significantly enhance the binding of vinculin head to the talin rod; decreasing the binding dissociation constant from previously reported μM range from test tube experiments (in the absence of force) 2 to nM range from our single-molecule assay.
This is reminiscent of effects reported for expression of the vinculin head domain [20] and suggests constitutive binding of vinculin-ΔEx20 to talin and other ligands of the vinculin head.
