Adhesion-mediated signaling

Cell adhesions with the ECM, as well as with each other, are essential for tissue scaffolding, as well as sensing the properties of the cell’s environment. The former, “physical” role, is intuitive, and broadly appreciated and documented, while the “signaling” mechanism is still poorly understood (Figure 1).

Figure 1

The adhesion-mediated signaling cycle. Cell-cell interaction as well as the properties of the ECM scaffold, such as composition, density, topography, rigidity, and associated external forces, induce the formation of cellular adhesion structures (“outside-in” effect). The resulting signaling cascades that follow, through the integrin adhesome, may in turn affect cell morphology, migration, proliferation, gene expression and differentiation.

It is interesting to note that the sensory function of FAs enables cells to identify multiple features of the matrix, some of which are chemical (namely, the molecular nature of the matrix, which can interact with different integrins) and others, “physical,” like ECM rigidity, geometry, topography, and ligand spacing. It is believed that cell interactions with the matrix, mediated by different integrins, can lead to different types of adhesions, and to the activation of diverse signaling processes, which involve such mechanisms as protein phosphorylation, activation of cytoskeletal regulators including different Rho GTPases and the like (Figure 2).

Figure 2

Paxillin is tyrosine phosphorylated in focal complexes (FXs) and focal adhesions (FAs), but not in fibrillar adhesions (FBs).  Porcine aortic endothelial cells were fixed and double-stained for paxillin and phospho (Y118) paxillin. Arrows indicate an FA and arrowheads an FB. Note the high level of phosphorylated paxillin in FXs and FAs, and its absence in FBs. The intensity profile of paxillin (blue line) or phosphorylated paxillin (pink line) along a line one-pixel wide, spanning both an FA and an FB, is shown. Bar, 10 μm.

Studies in our lab demonstrated different aspects of the cross-talk between the scaffolding components of cell adhesions, which contribute to the “mechanical” properties of the adhesions and the signaling components, which partake in the regulation of cell behavior and fate.