α-Catenin cytomechanics – role in cadherin-dependent adhesion and mechanotransduction

Abstract

The findings presented here demonstrate the role of a-catenin in cadherin-based adhesion and mechanotransduction in different mechanical contexts. Bead-twisting measurements in conjunction with imaging, and the use of different cell lines and a-catenin mutants reveal that the acute local mechanical manipulation of cadherin bonds triggers vinculin and actin recruitment to cadherin adhesions in an actin-and a-catenin-dependent manner. The modest effect of a-catenin on the two-dimensional binding affinities of cell surface cadherins further suggests that forceactivated adhesion strengthening is due to enhanced cadherincytoskeletal interactions rather than to a-catenin-dependent affinity modulation. Complementary investigations of cadherin-based rigidity sensing also suggest that, although a-catenin alters traction force generation, it is not the sole regulator of cell contractility on compliant cadherin-coated substrata.

Dynamic Visualization of α-Catenin Reveals Rapid, Reversible Conformation Switching between Tension States

“…The sensor is overexpressed in DLD1 and MDCK epithelial cells, but prior findings demonstrated that α–catenin-GFP overexpression in DLD1-R2/7 cells [15, 16] or in MDCK KD cells [16] did not affect cadherin-based mechanotransduction, vinculin and actin recruitment, or traction force generation [16]. Nor did cytosolic α–catenin depletion alter cadherin-based mechanotransduction [16].…”

“…At acutely stretched cell-cell junctions, the immediate, reversible conformational change further reveals that α-catenin behaves like an elastic spring in series with cadherin and actin. The force-dependent recruitment of vinculin—a principal α-catenin effector—to junctions requires the vinculin-binding-site of the α–catenin sensor [1, 12–16]. In cells, the relative rates of force-dependent α–catenin conformation switching and vinculin recruitment reveal that α–catenin activation and vinculin recruitment occur sequentially rather than in a concerted process, with vinculin accumulation being significantly slower.…”

Techniques to stimulate and interrogate cell–cell adhesion mechanics

“…This also demonstrates a new mechanotransduction pathway from cell–cell junctions to FAs, potentially through EGFR-PI3K mediated pathways. It is yet to be determined the extent to which the α -catenin-actin filament linkages participate in the force sensing and transducing process, despite the many previous reports confirming their tension-maintaining and conformation-altering roles [145, 158]. …”

Using magnets and magnetic beads to dissect signaling pathways activated by mechanical tension applied to cells

“…Another study by Kim et al used E-cadherin-coated magnetic beads to show a-catenin is an integral part of the force sensing apparatus at cell-cell junctions [28]. Other labs have also shown that vinculin, α-catenin, and actin are recruited to E-cadherin adhesions in response to force [29-31]…”