Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris

de Bruin, Alain; Caldelari, Reto; Williamson, Lina; Suter, Maja M; Hunziker, Thomas; Wyder, Marianne; Müller, Eliane J (2007). Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris. Experimental dermatology, 16(6), pp. 468-75. Oxford: Blackwell 10.1111/j.1600-0625.2007.00557.x

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We recently reported that the pathogenesis of pemphigus vulgaris (PV), an autoimmune blistering skin disorder, is driven by the accumulation of c-Myc secondary to abrogation of plakoglobin (PG)-mediated transcriptional c-Myc suppression. PG knock-out mouse keratinocytes express high levels of c-Myc and resemble PVIgG-treated wild-type keratinocytes in most respects. However, they fail to accumulate nuclear c-Myc and loose intercellular adhesion in response to PVIgG-treatment like wild-type keratinocytes. This suggested that PG is also required for propagation of the PVIgG-induced events between augmented c-Myc expression and acantholysis. Here, we addressed this possibility by comparing PVIgG-induced changes in the desmosomal organization between wild-type and PG knock-out keratinocytes. We found that either bivalent PVIgG or monovalent PV-Fab (known to trigger blister formation in vivo) disrupt the linear organization of all major desmosomal components along cell borders in wild-type keratinocytes, simultaneously with a reduction in intercellular adhesive strength. In contrast, PV-Fab failed to affect PG knock-out keratinocytes while PVIgG cross-linked their desmosomal cadherins without significantly affecting desmoplakin. These results identify PG as a principle effector of the PVIgG-induced signals downstream of c-Myc that disrupt the desmosomal plaque at the plasma membrane.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Caldelari, Reto, Williamson Ramirez, Lina, Suter, Maja, Hunziker, Thomas, Wyder, Marianne, Müller, Eliane Jasmine

ISSN:

0906-6705

Publisher:

Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:54

Last Modified:

05 Dec 2022 14:16

Publisher DOI:

10.1111/j.1600-0625.2007.00557.x

PubMed ID:

17518986

Web of Science ID:

000246683100002

URI:

https://boris.unibe.ch/id/eprint/23102 (FactScience: 39221)

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