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.