Desmosomes in acquired disease

Abstract

Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement functions to integrate adhesion and cytoskeletal elements of adjacent cells. The importance of this robust adhesion system is evident in numerous human diseases, both inherited and acquired, that occur when desmosome function is compromised. This review focuses on autoimmune and infectious diseases that impair desmosome function. In addition, we discuss emerging evidence that desmosomal genes are often misregulated in cancer. The emphasis of our discussion is placed on how human diseases inform our understanding of basic desmosome biology, and in turn, how fundamental advances in the cell biology of desmosomes may lead to new treatments for acquired diseases of the desmosome.

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

“…Desmosomes can also be affected in acquired diseases, which comprise epidermal autoimmune disorders and infections (Stahley and Kowalczyk 2015). Pemphigus is a family of diseases characterized by circulating autoantibodies that target desmosomal proteins and compromise cell -cell adhesion (Amagai 2010;Jennings et al 2011;Amagai and Stanley 2012).…”

Desmosome assembly, homeostasis, and desmosomal disease

“…[5][6][7] Further insight into the understanding of desmosome function and regulation has come from the study These membrane-bound, electron-dense structures link intermediate filaments (IFs) to the plasma membrane region between cells. 11 Ultrathin section electron microscopic observations demonstrate that desmosomes consist of a central electrondense midline between two plasma membranes of adjacent cells (desmoglea) and dense plaques, ie, the outer and inner dense plaques, forming the symmetrical desmosomal structure ( Figure 1A and B).…”

Structural basis of adhesive binding by desmocollins and desmogleins

“…These findings show that Dsg:Dsc heterodimers represent the fundamental adhesive unit of desmosomes and provide a structural framework for understanding desmosome assembly. (1)(2)(3). Dysfunction of desmosomes in inherited and acquired human diseases as well as in mouse genetic ablation studies causes characteristic defects in heart muscle and skin (3)(4)(5), demonstrating their importance in tissues that undergo mechanical stress.…”

“…(1)(2)(3). Dysfunction of desmosomes in inherited and acquired human diseases as well as in mouse genetic ablation studies causes characteristic defects in heart muscle and skin (3)(4)(5), demonstrating their importance in tissues that undergo mechanical stress. In electron micrographs, the hallmarks of mature desmosomes include a constant intermembrane distance of 280-340 Å, and apparently ordered electron-density in the intercellular space, often with a discrete midline connected by periodic cross-bridges to the cell membranes (6)(7)(8)(9).…”