Mechanical opening of the αE-catenin M-region gates afadin condensation in cardiomyocytes
In mechanically active tissues, cell-cell adhesions must withstand high and dynamic loads to maintain tissue integrity. The ability to detect and withstand load centers on the mechanosensitive adherens junction (AJ), which couples the actin networks of adjacent cells. The mechanosensor E-catenin responds to force by opening its Middle (M) region, revealing cryptic binding sites for adaptor…
Cell-cell adhesions in mechanically active tissues, like heart muscle cells, must endure high and fluctuating loads to preserve tissue structure. The mechanosensitive adherens junction (AJ), which connects the actin networks of neighboring cells, plays a crucial role in detecting and tolerating such loads. The E-catenin mechanosensor reacts to force by unwinding its Middle (M) region, exposing hidden binding sites for proteins such as afadin and vinculin.
Our research reveals that the afadin coiled-coil (CC) region attaches to the open E-catenin M-region with a weak grip and quick exchange, unlike vinculin's strong, long-lasting attachment. In cardiomyocytes, afadin's CC is essential for localization at high-load AJ sites, where it displays the rapid, responsive characteristics of a biomolecular condensate. Conversely, afadin's CC is not required for recruitment at low-load epithelial AJ sites, indicating that junctional load dictates afadin recruitment.
We suggest that force-gated opening of E-catenin initiates afadin condensate formation. This mechanism drives the remodeling of high-load AJ structures.
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