title: 150(th) anniversary series: Desmosomes and autoimmune disease, perspective of dynamic desmosome remodeling and its impairments in pemphigus.
abstract: Desmosomes are the most important intercellular adhering junctions that adhere two adjacent keratinocytes directly with desmosomal cadherins, that is, desmogleins (Dsgs) and desmocollins, forming an epidermal sheet. Recently, two cell-cell adhesion states of desmosomes, that is, "stable hyper-adhesion" and "dynamic weak-adhesion" conditions have been recognized. They are mutually reversible through cell signaling events involving protein kinase C (PKC), Src and epidermal growth factor receptor (EGFR) during Ca(2+)-switching and wound healing. This remodeling is impaired in pemphigus vulgaris (PV, an autoimmune blistering disease), caused by anti-Dsg3 antibodies. The antibody binding to Dsg3 activates PKC, Src and EGFR, linked to generation of dynamic weak-adhesion desmosomes, followed by p38MAPK-mediated endocytosis of Dsg3, resulting in the specific depletion of Dsg3 from desmosomes and acantholysis. A variety of pemphigus outside-in signaling may explain different clinical (non-inflammatory, inflammatory, and necrolytic) types of pemphigus. Pemphigus could be referred to a "desmosome-remodeling disease involving pemphigus IgG-activated outside-in signaling events".
authors: Department of Dermatology, Kizawa Memorial Hospital, Professor Emeritus Gifu University School of Medicine , Minokamo City, Gifu Prefecture , Japan.
authors: Yasuo
authors: Y
authors: Kitajima
mesh_terms: D000818:Animals; D003896:Desmosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008954:Models, Biological; D010392:Pemphigus / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D007633:Keratins
keywords: EGFR; PKC; Src; desmoglein 3; wound healing