Desmogleins are a family of proteins that play an important role in holding cells together within the body. They are found in various tissues, most notably in the skin, but also in the heart and other organs. These proteins act like a cellular “glue,” forming strong connections that contribute to the integrity and stability of tissues. Without these connections, cells cannot maintain their organized structures.
What Desmogleins Are
Desmogleins are proteins belonging to the cadherin superfamily. They are components of desmosomes, specialized cell structures that act as strong “spot welds” or “rivets” between neighboring cells. Desmosomes are important for tissues that experience mechanical stress, such as the skin, heart, and gastrointestinal lining.
There are four main types of desmogleins in humans: Desmoglein 1 (Dsg1), Desmoglein 2 (Dsg2), Desmoglein 3 (Dsg3), and Desmoglein 4 (Dsg4). These types are expressed differently across tissues and within layers of the same tissue. For instance, Dsg1 is found in the upper layers of the epidermis, while Dsg3 is found in the lower layers of the epidermis and throughout mucosal tissues. Dsg2 is expressed in simple epithelia and found in the lower layers of the epidermis and heart tissue. Dsg4 is found in the hair follicle and differentiated layers of the epidermis.
Desmogleins in Cell Adhesion
Desmogleins function by mediating direct cell-to-cell adhesion, contributing to the mechanical strength and integrity of tissues. Within desmosomes, desmogleins extend from the surface of one cell to bind with desmogleins or desmocollins (another type of desmosomal cadherin) on an adjacent cell. This interaction forms a strong intercellular bond. These adhesive interactions are dependent on calcium ions, which stabilize the protein structure and facilitate binding.
The cytoplasmic tails of desmogleins within the cell connect to a network of proteins called the desmosomal plaque, which links to the cell’s internal scaffolding, known as intermediate filaments. In skin cells, these intermediate filaments are composed of keratin. This connection to the cytoskeleton allows desmosomes to distribute mechanical forces across a wide area of cells, preventing them from tearing apart under stress. This arrangement ensures that tissues like the skin can withstand stretching and pulling.
Desmogleins and Disease
When desmogleins malfunction, it can lead to health conditions, such as autoimmune blistering diseases. The primary example is pemphigus, a group of rare autoimmune disorders where the body’s immune system produces antibodies that attack desmogleins. This disrupts adhesive bonds between skin cells, causing them to detach, a process known as acantholysis. This detachment results in fragile blisters and painful erosions on the skin and mucous membranes.
Pemphigus has two main forms: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). In PV, autoantibodies target Dsg3, or both Dsg3 and Dsg1, leading to blisters that can affect both the skin and mucous membranes, like the mouth. PF is characterized by autoantibodies against Dsg1, resulting in superficial blistering confined to the skin without affecting mucous membranes. Disease severity and affected areas often correlate with the targeted desmoglein type.
Beyond Disease: Other Roles
Beyond autoimmune conditions, desmogleins also play roles in other health conditions. For instance, desmoglein 1 is a target for bacterial toxins, such as those from Staphylococcus aureus. In conditions like staphylococcal scalded skin syndrome (SSSS) and bullous impetigo, bacterial exfoliative toxins cleave Dsg1, leading to loss of cell adhesion in the superficial skin layers. This results in widespread blistering and peeling, mimicking a burn.
Genetic mutations affecting desmogleins can also lead to inherited disorders. Mutations in the gene encoding Dsg1 have been linked to conditions such as striate palmoplantar keratoderma, which causes thickening of skin on palms and soles. Mutations in Dsg4 can result in hypotrichosis, a condition characterized by abnormal hair development. Dsg2, present in various tissues including the heart, has been linked to arrhythmogenic right ventricular cardiomyopathy, a heart condition.