Vinculin Phosphorylation at Tyr1065 Regulates Vinculin Conformation and Tension Development in Airway Smooth Muscle Tissues

Vinculin phosphorylation at residues Y100 and Y1065 is required for cellular force transmission

“…This finding is also supported by a recent FRET-based study describing that Y1065E vinculin molecules that are recruited to the membrane in smooth muscle cells after acetylcholine stimulation become activated, whereas Y1065F molecules remain in a closed conformation (Huang et al, 2014).…”

“…Phosphorylation at position 1065 is also associated with the lipid membrane interaction of the vinculin tail domain (Ito et al, 1983;Chandrasekar et al, 2005) and generation of cellular tractions (Diez et al, 2009;Küpper et al, 2010). Recent data have shown that phosphorylation of Y1065 is required for force generation in airway smooth muscle cells during contractile stimulation (Huang et al, 2011(Huang et al, , 2014. In addition, molecular dynamics simulations suggest that phosphorylation of Y100 and Y1065 favors the open and active conformation of vinculin (Golji et al, 2012), and more recently it has been shown that phosphorylation of the vinculin tail prevents its binding to vinculin head fragments .…”

Targeting integrin α5β1 ameliorates severe airway hyperresponsiveness in experimental asthma

“…rhChy modulates the interaction of smooth muscle cells with the ECM protein fibronectin. In addition to activation of the actinmyosin power stroke cycle, generation of tension by ASM depends on firm adhesion of the muscle to the underlying ECM (19,20). Mechanical force can regulate actin polymerization, stimulate the recruitment of the cytoskeletal linker and the signaling proteins focal adhesion kinase (FAK), paxillin, talin, vinculin, and α-actinin, and strengthen connections between these cytoskeletal adhesion complexes, integrins, and the ECM (21)(22)(23)(24)(25) (Figure 2A).…”

A helping hand: How vinculin contributes to cell-matrix and cell-cell force transfer

“…40 Recent studies using smooth muscle tissue further implicate the phosphorylation of Y1065 as a key mediator of vinculin function within FAs. 41 While our studies did not directly measure the phosphorylation state of Y1065, we speculate that, because the phosphorylation state affects the strength of the head-tail interaction, it is likely that the slope of the linear relationship between residence-time and force will be modulated by Y1065 phosphorylation. In this way, the phosphorylation state might be used to fine-tune the sensitivity of vinculin residence time wihtin FAs in response to applied CSK force, perhaps to rapidly control cell shape and migration speed and direction.…”