Broken hearts, woolly hair, and tattered skin: when desmosomal adhesion goes awry

Abstract

Desmosomal cadherins constitute the adhesive core of desmosomes. The different types of these cadherins are differentially expressed in a tissue specific as well as differentiation dependent manner. The skin and the heart are two examples of tissues whose vital functions require the ability to endure mechanical stress, and therefore, the integrity of desmosomal adhesion. When this adhesion is compromised via mutations in genes encoding desmosomal cadherins or associated plaque proteins, both tissues can suffer the consequences. Open questions revolve around whether the resulting phenotypes are solely due to physical disruption of cell adhesion, or whether these events are coupled with signaling mechanisms that influence many additional cellular processes. In this review, we focus on new developments in desmosomal adhesion with an emphasis on the skin, hair and heart.

iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death

“…Desmosomes are intercellular junctions that connect intermediate filaments to the cell surface and mediate strong cell-cell adhesion. They are particularly prominent in stratified squamous epithelia and myocardium (55,56). Accordingly, the junctional localization of iASPP is crucial for desmin intermediate filaments to locate at the intercalated discs in cardiomyocytes.…”

Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

“…These structures are prominent in tissues that experience an abundance of mechanical stress such as the epithelium and heart. In the heart, desmosomal components are present in the intercalated disc between cardiomyocytes (reviewed in Bazzi and Christiano 2007). The transmembrane, adhesive components of the desmosome are the desmosomal cadherins (desmoglein and desmocollin).…”

Desmosomes in the Uterine Epithelium of Noninvasive Skink Placentae

“…Desmosomal adhesion molecules comprise four desmogleins (Dsg1-4) and three desmocollins (Dsc 1-3), which are Ca 2þ -binding desmosomal cadherins responsible for the filamentous appearance of the extracellular region between two desmosomal plaques (Burdett, 1998;Bazzi and Christiano, 2007). Desmosomal cadherins exhibit tissue-specific patterns of expression; desmoglein-2 and desmocollin-2 are expressed in all desmosome-containing tissue (Eshkind et al, 2002), whereas expression of desmoglein-1 and -3 is largely restricted to stratified epithelial tissue and desmoglein-4 is present in the hair shaft (Jahoda et al, 2004).…”

“…In both rats and mice, the number of desmosomes in uterine epithelial cells decreases during implantation and early pregnancy (Illingworth et al, 2000;Preston et al, 2004), resulting from a redistribution of desmosomes to the apical portion of the lateral plasma membrane as pregnancy proceeds (Preston et al, 2004). Thus, a decrease in lateral adhesion takes place between adjacent uterine epithelial cells during this period, leading to a decrease in cytoskeletal binding (Bazzi and Christiano, 2007). Reduced desmosome numbers increases the plasticity of the uterine epithelium in preparation for implantation and so helps mediate the detachment of the epithelium (Illingworth et al, 2000;Preston et al, 2004).…”