title: One gene but different proteins and diseases: the complexity of dystonin and bullous pemphigoid antigen 1.
abstract: Since the immunochemical identification of the bullous pemphigoid antigen 230 (BP230) as one of the major target autoantigens of bullous pemphigoid (BP) in 1981, our understanding of this protein has significantly increased. Cloning of its gene, development and characterization of animal models with engineered gene mutations or spontaneous mouse mutations have revealed an unexpected complexity of the gene encoding BP230. The latter, now called dystonin (DST), is composed of at least 100 exons and gives rise to three major isoforms, an epithelial, a neuronal and a muscular isoform, named BPAG1e (corresponding to the original BP230), BPAG1a and BPAG1b, respectively. The various BPAG1 isoforms play a key role in fundamental processes, such as cell adhesion, cytoskeleton organization, and cell migration. Genetic defects of BPAG1 isoforms are the culprits of epidermolysis bullosa and complex, devastating neurological diseases. In this review, we summarize recent advances of our knowledge about several BPAG1 isoforms, their role in various biological processes and in human diseases.
authors.affiliation: Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Kseniia
authors.initials: K
authors.lastname: Künzli
authors.affiliation: Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Favre
authors.affiliation: Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Chofflon
authors.affiliation: Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Borradori
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002448:Cell Adhesion; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D000071821:Dystonin / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010391:Pemphigoid, Bullous / Q000235:genetics* / Q000276:immunology*; D051179:Plakins / Q000378:metabolism; D000072417:Protein Domains; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D001324:Autoantigens; C486268:DST protein, human; C095667:Dst protein, mouse; D000071821:Dystonin; D051179:Plakins; D020033:Protein Isoforms
keywords: BP230; BPAG1; Dystonia musculorum; bullous pemphigoid; dystonin; epidermolysis bullosa simplex; neurological disease; plakin; sensory autonomic neuropathy