Desmosomes: Structure, Pathologies, and Signaling Dynamics

Abstract

Desmosomes are a type of cell-to-cell junction, specialized intercellular structures that maintain tissue cohesion and structural integrity under mechanical stress. These complexes consist of transmembrane cadherins, including desmogleins and desmocollins, along with cytoplasmic proteins, such as plakoglobin, plakophilin, and desmoplakin, forming an adhesive network that links intermediate filaments. Beyond facilitating adhesion, desmosomes participate in cellular signaling, tissue remodeling, and physiological processes, allowing tissues to adapt to mechanical challenges while preserving organization. Desmosomes comprise transmembrane proteins that facilitate adhesion and cytoplasmic components that connect the adhesive interface to intermediate filaments to maintain structural organization. The expression of desmosomal proteins, including isotype and isoform variations, is adapted to the specific mechanical and functional needs of tissues, including stratified epithelia, cardiac tissue, and simple epithelia. Disruptions in desmosomal components are associated with various conditions, including autoimmune diseases, cardiac disorders such as arrhythmogenic cardiomyopathy, and cancers, where they influence adhesion and signaling pathways. This review reports numerous findings to provide a detailed understanding of desmosomes as structural connectors and regulatory hubs, emphasizing their importance in maintaining the tissue structure and coordinating biological processes across different systems.