Plectin in Epidermolysis Bullosa and Autoimmune, Bullous Diseases

Cytoskeletal networks are composed of microtubules, actin filaments, and intermediate filaments. Cytolinker proteins like plectin connect these cytoskeletal elements to membrane-based adhesion complexes. Plectin is abundantly expressed in a wide variety of mammalian cells and tissues including muscles, epithelia, and nerve tissues. In the skin it appears to be a component of both hemidesmosomes and desmosomes. The plectin polypeptide is approximately 500 kDa in size, and it features a multidomain structure, including an aminoterminal actin-binding domain and a carboxyterminal intermediate filament-binding domain. Mutations in the gene coding for PLEC lead to pathological conditions with many different phenotypes, referred to as hereditary recessive forms of epidermolysis bullosa simplex combined with muscle dystrophy (EBS-MD), pyloric atresia (EBS-PA), myasthenic syndrome (EBS-MD-MyS), and limb-girdle muscular dystrophy (LGMD2Q) as well as dominant phenotypes characterized as EBS-Ogna. In addition, rare forms of paraneoplastic pemphigus (PNP) and epidermolysis bullosa acquisita (EBA) occur as autoimmune, bullous diseases.