Desmosomes are specialized structures found between cells that function as robust adhesion points, playing a fundamental role in tissue mechanics and stability. They belong to a broader category of structures known as cell junctions, which physically link adjacent cells. Often described as “spot welds” or rivets, desmosomes ensure that cells remain tightly bound together, resisting forces that would otherwise pull them apart. This function is important in tissues that experience constant mechanical stress and require high tensile strength.
The Molecular Architecture of Desmosomes
The physical structure of a desmosome is a complex, multi-protein assembly organized into three main component layers. The core consists of transmembrane linker proteins, specifically Desmoglein and Desmocollin (members of the cadherin superfamily), which bridge the space between two adjacent cells. They physically interact with counterparts on the neighboring cell to establish the calcium-dependent cell-to-cell bond.
On the inside of the cell membrane, these transmembrane proteins anchor into a dense structure known as the cytoplasmic plaque. This plaque is composed of armadillo family proteins, including Plakoglobin and Plakophilins, which act as intermediate linkers connecting the desmosomal cadherins to Desmoplakin. Desmoplakin serves as the final anchor, extending from the plaque into the cell’s interior to tether the entire junction to the cytoskeleton. The specific filaments linked by Desmoplakin are the intermediate filaments, which provide tensile strength. In epithelial cells, the desmosome connects to Keratin filaments, while in heart muscle cells, it links to Desmin filaments, creating a continuous network linking the internal scaffolding of adjacent cells.
Primary Function: Maintaining Tissue Integrity
The primary function of desmosomes is to provide mechanical strength and stability to tissues. By linking the intermediate filament networks of adjacent cells, desmosomes form a continuous, load-bearing scaffold that extends throughout the entire tissue. This allows the tissue to withstand significant physical forces, such as pulling, stretching, and shearing, without tearing or rupturing.
When tension is applied, the force is distributed across the entire cellular interior via the intermediate filament network. This distribution prevents localized stress from causing the cell membrane to detach or the cell itself to tear. Desmosomes are far more robust in resisting mechanical stress compared to other cell junctions.
Key Tissues Where Desmosomes Are Important
Desmosomes are particularly abundant in tissues subjected to constant, high mechanical stress. The first is stratified squamous epithelium, which makes up the skin and the lining of the mouth and esophagus. The skin must resist constant abrasion, friction, and stretching.
The second area is the cardiac muscle, or myocardium, of the heart. Heart muscle cells contract rhythmically and powerfully, generating immense force. Desmosomes are concentrated at the intercalated discs, specialized junctions between heart muscle cells, where they ensure that the cells remain physically connected as the muscle fibers pull against each other during each heartbeat.
Desmosome Dysfunction and Associated Diseases
Disruptions to the desmosome’s structure or function can lead to severe diseases, often categorized as either autoimmune or genetic disorders.
Autoimmune Skin Blistering Diseases
The autoimmune skin blistering diseases, Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF), are caused by the body’s immune system attacking its own desmosomal proteins. In PV, autoantibodies primarily target Desmoglein 3, leading to blistering in the mucous membranes and deeper layers of the skin. PF involves autoantibodies targeting Desmoglein 1, causing blistering in the more superficial layers. This autoimmune attack compromises the adhesive function of the desmosomes, resulting in a loss of cell-to-cell cohesion, a process called acantholysis, and the subsequent formation of fragile blisters.
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Genetic defects in desmosomal proteins are the primary cause of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a serious heart condition. ARVC is often linked to inherited mutations in genes encoding Desmoplakin, Plakophilin-2, or Desmoglein-2. These mutations weaken the desmosomes in the heart muscle, leading to the gradual loss of heart muscle cells under mechanical stress. Over time, the dead heart muscle tissue is replaced by fibrofatty scar tissue, which disrupts the heart’s electrical signaling. This structural and electrical compromise results in irregular heart rhythms, or arrhythmias, which can lead to sudden cardiac death.