Desmosome regulation and signaling in disease

Abstract

Desmosomes are cell-cell adhesive organelles with a well-known role in forming strong intercellular adhesion during embryogenesis and in adult tissues subject to mechanical stress, such as the heart and skin. More recently, desmosome components have also emerged as cell signaling regulators. Loss of expression or interference with the function of desmosome molecules results in diseases of the heart and skin and contributes to cancer progression. However, the underlying molecular mechanisms that result in inherited and acquired disorders remain poorly understood. To address this question, researchers are directing their studies towards determining the functions that occur inside and outside of the junctions and the extent to which functions are adhesion-dependent or independent. This review focuses on recent discoveries that provide insights into the role of desmosomes and desmosome components in cell signaling and disease; wherever possible, we address molecular functions within and outside of the adhesive structure.

Cell–Cell Junctions Organize Structural and Signaling Networks

“…Disruption of any part of the desmosomal complex leads to fragility, blistering and, in extreme cases, sloughing of the entire epidermis (reviewed in Kottke et al 2006; Haines and Lane 2012; Broussard et al 2015). The lesion site in the epidermis depends on which desmosomal cadherin is disrupted.…”

“…Dsg and Dsc interact with two members of the Armadillo family of proteins, plakoglobin and plakophilin (Broussard et al 2015). Plakoglobin binds directly to Dsg and Dsc, and is required for desmosome assembly by clustering Dsg/Dsc in the plasma membrane; plakoglobin can also substitute for beta-catenin in the AJ (Bierkamp et al 1999; Bornslaeger et al 2001; Acehan et al 2008; Lewis et al 1997; Kowalczyk et al 1997).…”

Molecular organization of the desmosome as revealed by direct stochastic optical reconstruction microscopy

“…The importance of desmosome-mediated adhesion is evidenced by the numerous human diseases that result when desmosomes are compromised, manifesting in epidermal fragility, cardiomyopathies and cancers (Broussard et al, 2015;.…”

Studies on cell junctions in an ex vivo human lung infection model

“…Desmosomes are primarily found in epithelial cells of the skin [135,136] as well as in non-epithelial tissues such as the cardiac muscle [137][138][139]. They provide mechanical stability and strong adhesion between cells [140,141] contributing to resist shearing forces.…”