Desmosomal Cadherins and Intercellular Adhesion Mechanisms

Desmosomal cadherins are specialised adhesion proteins that mediate strong cell–cell contacts in tissues exposed to mechanical stress, such as epidermis and myocardium. These cadherins—desmogleins and desmocollins—assemble into desmosomes, intercellular junctions that anchor to the intermediate filament cytoskeleton and confer tensile rigidity. Beyond static adhesion, desmosomal cadherins participate in mechanotransduction, coordinating biochemical signals with cytoskeletal dynamics. They also intercommunicate with adherens junctions and tight junctions to regulate barrier formation, tissue stratification and morphogenesis. Dysregulation of desmosomal cadherins underlies a range of pathologies from blistering skin diseases to cardiac arrhythmias and contributes to tumour progression and metastasis. Recent advances have elucidated the molecular interplay between cadherin isoforms, associated plaque proteins and the cytoskeleton, shedding light on both the mechanical load-bearing function of desmosomes and their emerging roles in signal transduction and cell fate regulation.

Research from Nature Portfolio

Recent studies have revealed how classical cadherins integrate with desmosomal machinery to control tissue architecture. One investigation demonstrated that E-cadherin tunes epidermal junctional tension by modulating EGFR signalling, thereby dictating the spatial assembly of tight junctions and desmosomes during barrier formation. Complementary work using FRET-based tension sensors showed that desmoplakin remains mechanically unloaded under steady-state conditions but becomes transiently stressed upon externally applied forces, confirming that desmosomes act as dynamic stress-absorbing elements. In parallel, mechanistic analysis of desmoglein 1 uncovered its interaction with the dynein light chain Tctex-1 and the actin-nucleating complex cortactin–Arp2/3, which drives perijunctional actin polymerisation and basal cell delamination during epidermal stratification, highlighting a morphogenetic role for desmosomal cadherins beyond adhesion.

Desmosomal Cadherins and Intercellular Adhesion Mechanisms publication trend

The graph below shows the total number of articles in desmosomal cadherins and intercellular adhesion mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Desmosome: A specialised intercellular junction that couples desmosomal cadherins to intermediate filaments, providing mechanical strength to tissues.

Desmoglein / Desmocollin: Transmembrane cadherins forming the adhesive core of desmosomes via homophilic extracellular interactions.

Cadherin: Calcium-dependent adhesion proteins that mediate homophilic binding between adjacent cells.

Intermediate filament: Cytoskeletal polymers that anchor to desmosomes and confer tensile resilience to cells.

Adherens junction: Cell–cell adhesion complexes composed of classical cadherins linked to the actin cytoskeleton.

Mechanotransduction: Conversion of mechanical stimuli into biochemical signals within cells and tissues.

Actin cytoskeleton: Network of actin filaments that supports cell shape, adhesion dynamics and motility.

FRET: Förster resonance energy transfer, a technique to measure molecular proximity and mechanical tension in living cells.

References

1. A complex of cadherin 17 with desmocollin 1 and p120-catenin regulates colorectal cancer migration and invasion according to the cell phenotype. Journal of Experimental & Clinical Cancer Research (2024).
2. Plakophilin 3 facilitates G1/S phase transition and enhances proliferation by capturing RB protein in the cytoplasm and promoting EGFR signaling. Cell Reports (2023).
3. Cytoskeletal anchorage of different Dsg3 pools revealed by combination of hybrid STED/SMFS-AFM. Cellular and Molecular Life Sciences (2023).
4. E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nature Communications (2017).
5. Mechanical loading of desmosomes depends on the magnitude and orientation of external stress. Nature Communications (2018).
6. Desmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination. Nature Communications (2018).
7. Desmosomes: Essential contributors to an integrated intercellular junction network. F1000Research (2019).