Through the Microscope Lens: Investigating the Mechanisms of Desmosome Disruption in Pemphigus

Desmosomes are adhesive cell-cell junctions that are necessary for resisting mechanical stress and maintaining the integrity of the epidermis and other epithelial tissues. Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by autoantibodies against desmosomal cadherins known as desmogleins. PV autoantibodies cause the loss of cell-cell adhesion and subsequent blistering of the skin and oral mucosa through a variety of mechanisms, including steric hindrance of desmoglein adhesive interactions, destabilization of desmosome assembly and disassembly dynamics, and dysregulated cell signaling. We focus this review on emerging literature and highlight microscopy techniques that have been used to study the structural changes that occur during desmosome disassembly in PV. Furthermore, we discuss recent findings demonstrating that the desmosome forms a complex with the endoplasmic reticulum and highlight the potential role of this multiorganelle complex in mediating desmosome disassembly and signaling in response to cell adhesion stress.