{"doi":"10.1083/jcb.153.4.823","title":"A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris","abstract":"<jats:p>In pemphigus vulgaris (PV), autoantibody binding to desmoglein (Dsg) 3 induces loss of intercellular adhesion in skin and mucous membranes. Two hypotheses are currently favored to explain the underlying molecular mechanisms: (a) disruption of adhesion through steric hindrance, and (b) interference of desmosomal cadherin-bound antibody with intracellular events, which we speculated to involve plakoglobin. To investigate the second hypothesis we established keratinocyte cultures from plakoglobin knockout (PG−/−) embryos and PG+/+ control mice. Although both cell types exhibited desmosomal cadherin-mediated adhesion during calcium-induced differentiation and bound PV immunoglobin (IgG) at their cell surface, only PG+/+ keratinocytes responded with keratin retraction and loss of adhesion. When full-length plakoglobin was reintroduced into PG−/− cells, responsiveness to PV IgG was restored. Moreover, in these cells like in PG+/+ keratinocytes, PV IgG binding severely affected the linear distribution of plakoglobin at the plasma membrane. Taken together, the establishment of an in vitro model using PG+/+ and PG−/− keratinocytes allowed us (a) to exclude the steric hindrance only hypothesis, and (b) to demonstrate for the first time that plakoglobin plays a central role in PV, a finding that will provide a novel direction for investigations of the molecular mechanisms leading to PV, and on the function of plakoglobin in differentiating keratinocytes.</jats:p>","journal":"The Journal of Cell Biology","year":2001,"id":43102,"datarank":8.655624937698057,"base_score":5.247024072160486,"endowment":5.247024072160486,"self_citation_contribution":0.787053610824073,"citation_network_contribution":7.868571326873984,"self_endowment_contribution":0.787053610824073,"citer_contribution":7.868571326873984,"corpus_percentile":null,"corpus_rank":null,"citation_count":189,"citer_count":163,"citers_with_citation_signal":141,"citers_with_endowment":141,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":205344,"name":"Alain de Bruin","orcid":null,"position":1,"is_corresponding":false},{"id":205345,"name":"Dominique Baumann","orcid":null,"position":2,"is_corresponding":false},{"id":205346,"name":"Maja M. 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