29.9:
Tension Response at Adherens Junctions
Tissues like the skin and intestinal epithelium are constantly experiencing external mechanical forces such as pinching or stretching.
The adherens junctions that anchor these epithelial cells together can change dynamically in response to such mechanical tension. This conversion of mechanical stimuli into biochemical changes is called mechanotransduction.
In these cells, the adherens junctions form a continuous zone of attachment —the adhesion belt — comprising large clusters of cadherins, catenins, and actomyosin contractile bundles.
The alpha-catenins at these junctions act as mechanosensory proteins that change conformation in response to mechanical tension.
When increased contractile forces pull the actin filaments, the alpha-catenin changes from the folded to the unfolded conformation.
This unfolding opens a cryptic binding site to vinculin, a cytoskeletal binding protein that remains in its closed, inactive form in the cytoplasm.
Upon binding alpha-catenin, vinculin changes conformation to its open, active form.
The active vinculin promotes the recruitment of additional actin filaments to the site, thus strengthening the junction and distributing the force across the cells.
29.9:
Tension Response at Adherens Junctions
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains that can bind various actin-binding proteins like vinculin, afadin, and α-actinin. Under normal conditions, the α-catenin is folded, and these VH binding domains are inaccessible. The N-terminal is anchored to β-catenin, and the C-terminal end is bound to the actomyosin cytoskeleton. When the internal tensile force increases and myosin II pulls on the actin filament, the bound α-catenin unfolds, and its VH domains become available for binding.
Role of Vinculin in Mechanotransduction
Vinculin is another dynamic protein with a head and a tail domain joined by a flexible neck region. In its inactive form, the head and tail domains interact with each other, preventing the binding of other proteins. However, when the exposed VH domain of α-catenin binds the vinculin head domain, the protein changes to an open conformation. The free tail domain can now bind actin and recruit more actin filaments to this junction. The open neck region also binds various proteins that regulate actin polymerization, such as Arp2/3, thus dynamically reorganizing the actin cytoskeleton in response to mechanical stress.
Suggested Reading
- Charras, Guillaume, and Alpha S. Yap. "Tensile forces and mechanotransduction at cell–cell junctions." Current Biology 28.8 (2018): R445-R457.
- Goldmann, Wolfgang H. "Role of vinculin in cellular mechanotransduction." Cell biology international 40.3 (2016): 241-256.
- Pinheiro, Diana, and Yohanns Bellaiche. "Mechanical force-driven adherens junction remodeling and epithelial dynamics." Developmental cell 47.1 (2018): 3-19.