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.
Skip Nav Destination
Article navigation
14 May 2001
Article|
May 14 2001
A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris
Reto Caldelari,
Reto Caldelari
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Search for other works by this author on:
Alain de Bruin,
Alain de Bruin
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Search for other works by this author on:
Dominique Baumann,
Dominique Baumann
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Search for other works by this author on:
Maja M. Suter,
Maja M. Suter
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Search for other works by this author on:
Christiane Bierkamp,
Christiane Bierkamp
bCentre de Biologie du Developpement, 31062 Toulouse, France
Search for other works by this author on:
Vreni Balmer,
Vreni Balmer
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Search for other works by this author on:
Eliane Müller
Eliane Müller
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Search for other works by this author on:
Reto Caldelari
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Alain de Bruin
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Dominique Baumann
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Maja M. Suter
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Christiane Bierkamp
bCentre de Biologie du Developpement, 31062 Toulouse, France
Vreni Balmer
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
Eliane Müller
aInstitute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland
R. Caldelari and A. de Bruin contributed equally to this work.
Abbreviations used in this paper: Dsg, desmoglein; E-cad, E-cadherin; GFP, green fluorescent protein; IF, immunofluorescence; nhIgG, normal human IgG; PV, pemphigus vulgaris; WB, Western blot.
Received:
August 07 2000
Revision Requested:
March 23 2001
Accepted:
March 23 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Cell Biol (2001) 153 (4): 823–834.
Article history
Received:
August 07 2000
Revision Requested:
March 23 2001
Accepted:
March 23 2001
Connected Content
Citation
Reto Caldelari, Alain de Bruin, Dominique Baumann, Maja M. Suter, Christiane Bierkamp, Vreni Balmer, Eliane Müller; A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris. J Cell Biol 14 May 2001; 153 (4): 823–834. doi: https://doi.org/10.1083/jcb.153.4.823
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
See also
Email alerts
Advertisement
Advertisement