Cells will form adhesive interactions with other cells as well as with ECM. Most of these interactions utilize a different set of proteins, although integrins have been found to interact with some cell adhesion proteins. An example of a cell-cell interaction with many similarities to a cell-ECM interaction, but using different adhesion molecules, is the desmosome. Like its basal-lamina-attached counterpart, the hemidesmosome, the desmosome is found in epithelial sheets, and its purpose is to link cells together so that pressure is spread across many cells rather than concentrated on one or a few. Desmosomes are necessary for the structural integrity of epithelial layers, and are the most common cell-cell junction in such tissues. The primary structural characteristic of the hemidesmosome, the dense plaque reinforcing the intracellular side of the adhesion, is also found in desmosomes, although it is composed of different proteins. In desmosomes, the plaque is composed primarily of plakoglobins and desmoplakins. The plakoglobins connect the adhesion molecules to the desmoplakins, and the desmoplakins link to intermediate laments such as keratin.
Figure 12. Desmosomes connect the intermediate laments of adjacent cells across adhesion molecules strengthened by a protein plaque. Desmoglein and desmocollin, the adhesion molecules are members of the cadherin family, and the reinforcing plaque contains plakoglobin, which connects the adhesion molecules to the IF linker, desmoplakin.
Another similarity to hemidesmosomes, and one predicted by the involvement of keratin, is the permanence of desmosomes. On the other hand, a key difference between the two types of adhesions is the adhesion proteins involved. The major proteins of the desmosome are desmoglein and desmocollin, both of which are members of the cadherin superfamily of Ca2+-dependent adhesion molecules.
Mutations in desmoplakin (on chromosome 6p24) are linked to Carvajal syndrome (also known as dilated cardiomyopathy with woolly hair and keratoderma). Patients are born with woolly hair, and palmoplantar keratoderma appears within the first year. Dilation of the left ventricle and attending weakness in contractility may lead to death from heart failure in teenage years.
Pemphigus vulgaris is another rare disease involving dysfunction of desmosomes. It is an autoimmune disease targeted to the patient’s own desmoglein proteins. The reduced epithelial adhesion leads to blistering of skin and mucous membranes.