All living tissue requires cells to adhere to each other and to their surrounding environment. This necessity is managed by specialized cell junctions, which are complex protein assemblies that physically link cells. Among the most robust are anchoring junctions, which function like molecular rivets to distribute mechanical stress across tissues. Desmosomes and hemidesmosomes are two prominent types of anchoring junctions that maintain the integrity of tissues subjected to constant physical forces.
The Core Function of Desmosomes
Desmosomes facilitate strong, stable adhesion between adjacent cells. They are often described as spot-like welds that mechanically link two cells together across a small intercellular space. This cell-to-cell connection is necessary in tissues that endure high mechanical stress, such as the epidermis of the skin and the cardiac muscle. Desmosomes ensure cells remain tightly bound, allowing the tissue to stretch and resist pulling forces.
The structure centers on a dense, protein-rich cytoplasmic plaque inside the cell. Specialized adhesion molecules from the cadherin family, Desmoglein and Desmocollin, extend from this plaque. These molecules span the cell membrane and interlock with counterparts from the neighboring cell in the extracellular space. This connection anchors the intermediate filaments of the cytoskeleton—primarily keratin filaments—to the cell membrane, spreading mechanical tension throughout the cell.
The Role of Hemidesmosomes
Hemidesmosomes anchor a cell not to another cell, but to the underlying non-cellular material. They attach the basal layer of epithelial cells to the basement membrane, a specialized sheet of extracellular matrix. This cell-to-matrix connection provides the foundation necessary for epithelial tissues, such as the lining of the digestive tract and the skin, to remain securely attached to the underlying connective tissue.
These junctions are described as “half-desmosomes” because they connect only one cell to the matrix. The transmembrane adhesion molecules used are from the integrin family, primarily the \(\alpha6\beta4\) integrin, which binds to basement membrane components like laminin. Inside the cell, the integrin is linked to the keratin intermediate filaments by proteins like Plectin. This creates a continuous structural bridge from the extracellular matrix into the cell’s internal scaffolding.
Key Structural Differences
The fundamental difference lies in their symmetry and target. Desmosomes are symmetrical, with both adjacent cells contributing identical components to form the junction (cell-to-cell adhesion). Conversely, hemidesmosomes are asymmetrical, as only the single cell contributes the internal plaque and transmembrane proteins to connect with the external basement membrane (cell-to-extracellular matrix adhesion).
Adhesion Molecules
The adhesion molecules used by each junction represent a major point of contrast. Desmosomes utilize Cadherins (Desmoglein and Desmocollin), which are calcium-dependent molecules that bind across the gap between two cells. Hemidesmosomes use Integrins, which are specialized receptors that recognize and bind to specific proteins found in the extracellular matrix, such as laminin.
Internal Plaque Architecture
The arrangement of the internal linking proteins also differs, even though both junctions connect to the intermediate filament network (often keratin). In desmosomes, the cytoplasmic plaque includes proteins like Desmoplakin, which directly links the Cadherins to the keratin filaments. In hemidesmosomes, the plaque includes Plectin and Bullous Pemphigoid Antigen 1 (BPAG1), which act as adaptors to bridge the \(\alpha6\beta4\) Integrin to the keratin filaments.
Implications in Health
Dysfunction in either desmosomes or hemidesmosomes can lead to severe tissue fragility. When desmosomes fail, the resulting loss of cell-to-cell adhesion causes tissue layers to separate. This is observed in autoimmune blistering diseases like Pemphigus Vulgaris, where antibodies attack desmosomal cadherins, causing the outer layers of the skin and mucous membranes to blister. Desmosome defects are also implicated in inherited heart conditions, such as Arrhythmogenic Cardiomyopathy, which leads to structural damage in the cardiac muscle.
Failure of hemidesmosomes compromises the secure attachment of the epithelium to its underlying foundation. The autoimmune disease Bullous Pemphigoid involves antibodies targeting hemidesmosomal proteins, leading to a separation of the epidermis from the dermis and forming large, tense blisters. Inherited conditions like certain forms of Epidermolysis Bullosa, involving mutations in hemidesmosome components, also result in skin fragility and blistering.