Aspects of the structure and assembly of desmosomes

Abstract

Desmosomes are found principally in epithelial cells and consist of disc-like plaques, the extracellular face of which is paired with that of a neighbouring cell. There is increasing evidence that desmosomes are adhesive structures, and that two types of desmosomal glycoproteins, the desmogleins (Dsg) and desmocollins (Dsc), both Ca2+-binding cadherin-like molecules, perform this role in adhesion through interaction of their extracellular domains. A number of isoforms of Dsg and Dsc are present in specific tissues. The cytoplasmic side of the plaque is attached to intermediate filaments through desmoplakin, a major plaque protein. Also associated with desmosomes are plakoglobin and β-catenin, suggesting that the adhesive function of desmosomes might be mediated by signal transduction. Formation of desmosomes can be studied by growing epithelial cells in low-Ca2+ medium (LCM, < 0.1 mM), where desmosomal proteins are either synthesized but not assembled, or form partially assembled but unstable half-desmosomes. Addition of Ca2+ (to about 2 mM) initiates cell contact and, in the case of half-desmosomes, leads to stabilization by incorporation into membranes and formation of typical paired structures. In cases where such pre-assembled structures are not formed, recruitment of desmosomal proteins appears to occur by vesicular transport of desmocollins and desmogleins to the cell surface, where association is made with plakoglobin and later, with desmoplakin. Although much remains to be learned of the assembly process, specific interacting domains of the molecular components are being recognized. Desmosome assembly is part of a coordinated pattern of junction formation which accompanies the establishment of cell polarity, resulting in differentiation of apical and basolateral cell surfaces. Desmosomes are now being regarded, not as static and inert structures, but as membrane specializations linked to systems involved in cell-cell communication as well as adhesion.