What are some diseases that are associated with desmosomes?

Posted on: 10th May 2023


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One example of an adhesion molecule is a desmosomal cadherin. Desmosomes contain two cadherins, desmoglein and desmocollin. The extracellular doamins of these transmembrane proteins form the adhesive interface of the desmosome. The cytoplasmic tails anchor proteins like plakoglobin and plakophilins to the desmosomal plaque. When the cytosolic domains of desmosomes bind to adapter proteins, like plakoglobin and plakophilins, they then bind to desmoplakin adapters. Desmoplakin form the thick cytoplasmic plaque that is typical of desmosomes and mediate plaque binding to intermediate filaments (Lodish, et al., 2021). By mediating cell to cell adhesion and cytoskeletal connections, desmosomes integrate cells within tissues. Desmosomes are responsible for maintaining tissue integrity, resisting mechanical stress, and are essential for tissue morphogenesis (Kowalczyk & Green, 2013).

What are some diseases that are associated with desmosomes?

Works Cited
Kowalczyk, A. P., & Green, K. J. (2013). Structure, Function and Regulation of Desmosomes. Progress in Molecular Biology and Translational Science, 95-118.
Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Bretscher, A., Ploegh, H., . . . Amon , A. (2021). Molecular Cell Biology. W.H. Freeman.

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Diseases That Are Associated with Desmosomes

A number of diseases are associated with desmosome dysfunction. These include pemphigus vulgaris, Bullous pemphigoid, and epidermolysis bullosa. In pemphigus vulgaris, desmosome-deficient epidermal cells aggregate in dendritic and epithelial blisters. The lack of desmosomes prevents cells from adhering to each other. The defective cell-cell adhesion causes an imbalance between proliferation and differentiation in the skin. This imbalance leads to abnormal proliferation of keratinocytes that produces abnormal secretions and blister formation (Hammers & Stanley, 2016).

In bullous pemphigoid, a protein called BSL-1/NEMO interferes with desmosomal attachment. This results in impaired keratinocyte migration and increased cell death (Spindler & Waschke, 2018). Similarly, "epidermolysis bullosa" is a group of inherited disorders that are characterized by extreme desmosome-dependent skin blistering. The abnormal actin ring structure of pili and defective keratinocyte cytoskeleton attachment cause epidermal detachment from the underlying dermal layer in this disease (Spindler & Waschke, 2018).

Conditions like dermatomyositis and Sjögren syndrome have been linked to a defect in desmosome structure. In these conditions, the body is unable to maintain proper concentrations of calcium within the cell. This results in an inability to form a plaque around the cell membrane and loss of adhesion between cells (Migkos et al., 2018). A significant amount of research has been conducted on the involvement of desmosomes in cancer metastasis. Much of the research has been conducted on glioma, which is a malignant tumor in the nervous system. In many tumours, a process called "canalization" occurs. This process consists of the formation of small, narrow channels in the plasma membrane that allows cancer cells to escape from immune surveillance and invade surrounding tissues. This process is important for cancer cell proliferation and dissemination throughout organs.

Image (Hammers & Stanley, 2020):



Hammers, C. M., & Stanley, J. R. (2016). Mechanisms of Disease: Pemphigus and Bullous Pemphigoid. Annual Review of Pathology: Mechanisms of Disease, 11(1), 175–197. https://doi.org/10.1146/annurev-pathol-012615-044313

Hammers, C. M., & Stanley, J. R. (2020). Recent advances in understanding pemphigus and bullous pemphigoid. Journal of Investigative Dermatology140(4), 733-741. https://doi.org/10.1016/j.jid.2019.11.005

Migkos, M. P., Sarmas, I., Somarakis, G. Α., Voulgari, P. V., Tsamis, K. I., & Drosos, A. A. (2018). Sjögren Syndrome Associated with Inflammatory Muscle Diseases. Mediterranean Journal of Rheumatology, 29(2), 92–96. https://www.mjrheum.org/june-2018/showreferences792/1/showfulltext792/1/newsid792/129

Spindler, V., & Waschke, J. (2018). Pemphigus—A Disease of Desmosome Dysfunction Caused by Multiple Mechanisms. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.00136


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