{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:54:06Z","timestamp":1771530846905,"version":"3.50.1"},"reference-count":58,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,5,14]]},"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\u2212\/\u2212) 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\u2212\/\u2212 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\u2212\/\u2212 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>","DOI":"10.1083\/jcb.153.4.823","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:46:23Z","timestamp":1027701983000},"page":"823-834","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":157,"title":["A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris"],"prefix":"10.1083","volume":"153","author":[{"given":"Reto","family":"Caldelari","sequence":"first","affiliation":[{"name":"aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"de Bruin","sequence":"additional","affiliation":[{"name":"aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Baumann","sequence":"additional","affiliation":[{"name":"aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja M.","family":"Suter","sequence":"additional","affiliation":[{"name":"aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Bierkamp","sequence":"additional","affiliation":[{"name":"bCentre de Biologie du Developpement, 31062 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vreni","family":"Balmer","sequence":"additional","affiliation":[{"name":"aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliane","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2001,5,14]]},"reference":[{"key":"2023072211424205300_Amagai1995","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/1523-1747.ep12613668","article-title":"Adhesion molecules. 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