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| A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris |
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| Author(s): Caldelari R, de Bruin A, Baumann D, Suter MM, Bierkamp C, Balmer V, Muller E |
| Source: JOURNAL OF CELL BIOLOGY Volume: 153 Issue: 4 Pages: 823-834 Published: MAY 14 2001 |
| Times Cited: 86 References: 58 |
| Abstract: 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 Pike 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Muller, E (reprint author), Univ Bern, Inst Anim Pathol, Langgass Str 122, CH-3012 Bern, Switzerland |
Addresses:
1. Univ Bern, Inst Anim Pathol, CH-3012 Bern, Switzerland
2. Ctr Dev Biol, F-31062 Toulouse, France |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA |
| Subject Category: Cell Biology |
| IDS Number: 433QH |
| ISSN: 0021-9525 |
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