- Adherens junctions are essential cell-cell adhesion complexes that provide mechanical strength and stability to tissues. Found in nearly all solid tissues, these specialized structures are particularly abundant in epithelial and endothelial cell layers, where they form continuous adhesion belts just below tight junctions. Unlike the sealing function of tight junctions, adherens junctions primarily serve as structural anchors, connecting neighboring cells through robust protein networks that transmit mechanical forces and maintain tissue integrity. Their dynamic nature allows tissues to withstand stress while remaining flexible enough for remodeling during processes like embryonic development and wound healing.
- At their core, adherens junctions consist of cadherin family proteins that span the intercellular space. Classical cadherins like E-cadherin in epithelia and VE-cadherin in endothelia mediate calcium-dependent homophilic binding between adjacent cells. These transmembrane proteins link to the actin cytoskeleton through a complex of cytoplasmic adaptor proteins, including β-catenin, α-catenin, and p120-catenin. This connection creates a mechanical continuum that distributes forces across cell sheets, allowing tissues to function as coordinated units rather than collections of individual cells. The actin-binding protein vinculin further strengthens this linkage, providing additional stability under tension.
- The functions of adherens junctions extend far beyond simple adhesion. They play crucial roles in establishing and maintaining cell polarity by organizing apical-basal domains in epithelial tissues. During morphogenesis, dynamic changes in adherens junctions facilitate tissue folding and tube formation through controlled cell shape changes. These junctions also serve as signaling hubs, with catenins participating in Wnt signaling pathways that regulate cell proliferation and differentiation. Remarkably, adherens junctions can sense and respond to mechanical tension, adjusting their composition and strength to match physiological demands—a property critical for tissues like the heart and blood vessels that experience constant mechanical stress.
- Different tissues exhibit specialized forms of adherens junctions adapted to their specific needs. In epithelial sheets, adherens junctions form continuous belts that coordinate collective cell movements during development and repair. Endothelial cells contain both belt-like junctions and spot-like junctions called “focal adherens junctions” that allow selective permeability while maintaining barrier function. Cardiac muscle cells feature unique hybrid adherens junctions that combine features of intercalated discs and classical epithelial junctions, enabling the heart to withstand rhythmic contractions. Neurons utilize N-cadherin-based adherens junctions at synapses, where they contribute to synaptic plasticity and stability.
- Dysregulation of adherens junctions underlies numerous pathological conditions. Loss of E-cadherin function is a hallmark of epithelial-mesenchymal transition (EMT), a key step in cancer metastasis. Mutations in cadherin or catenin genes are associated with various diseases, including familial gastric cancer (E-cadherin mutations) and arrhythmogenic right ventricular cardiomyopathy (plakoglobin mutations). Inflammatory conditions like atherosclerosis involve VE-cadherin dysfunction in endothelial junctions. Even neurological disorders such as autism spectrum disorders have been linked to abnormalities in neuronal cadherin function.
- Current research on adherens junctions focuses on their mechanosensitive properties and role in disease progression. Advanced imaging techniques reveal how these junctions respond to mechanical forces at nanoscale resolution. Scientists are developing cadherin-targeting therapies for cancer and cardiovascular diseases, with some antibody-based treatments already in clinical trials. Tissue engineering approaches harness the self-organizing properties of adherens junctions to create more physiologically accurate organoids and artificial tissues. There is growing interest in how microbial pathogens manipulate adherens junctions during infection, potentially revealing new antimicrobial targets.
- Future directions in adherens junction research include exploring their role in immune cell interactions and developing biomaterials that mimic their adhesive properties for regenerative medicine. The emerging field of mechanobiology continues to uncover how these junctions translate physical forces into biochemical signals. As our understanding of these fundamental structures grows, so does their potential as therapeutic targets for conditions ranging from metastatic cancer to chronic inflammatory diseases, making adherens junctions a vibrant area of biomedical research.
