Mechanosignaling

How are proteins recruited to focal adhesion sites?

The chronological order of protein recruitment into focal adhesions leads to the concept of sequential assembly. Accordingly, the exact composition of each elongating adhesions is dependent on their age. The dynamics of component recruitment within individual adhesions has been shown to depend on the rate of lamellipodial protrusion within a given area [1]. Adhesions initially contain αVβ3 integrins, talin, paxillin and low levels of vinculin and focal adhesion kinase (FAK) [2] (reviewed in [3]).

Among the early components, FAK is a well-established mechanotransducer [4], that can bind Src [5], become activated [6] and serves to phosphorylate scaffolding proteins such as paxillin [7] and p130Cas [8] (reviewed in [9]). It also suppresses Rho activity to promote adhesion turnover [10]. p130CAS, in turn, facilitates formation of Rac-GEF complex, leading to membrane protrusion and ruffling [11] (reviewed in [12]). Paxillin contains several protein interaction domains that bind to numerous signaling molecules (e.g. kinases, phosphatases, Rho family of GTPases), adhesion molecules (e.g. α-integrin [13][14]) and actin-binding proteins (e.g. vinculin and parvin)[15] (reviewed in [16]).

The recruitment of vinculin along with talin promotes the clustering of activated integrins, forming a flexible bridge between the receptors and the actin network [17][18]. Vinculin also contributes to mechanical stability by regulating contractile stress generation [19]. Thus, the later stages can be distinguished by the presence of higher levels of vinculin, α-actinin, FAK, VASP and low levels of zyxin (reviewed in [2]).

References

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