Plakoglobin but Not Desmoplakin Regulates Keratinocyte Cohesion Via Modulation of P38MAPK Signaling

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2014 Jan 21

PMID 24441103

Citations 24

Authors

Volker Spindler

Carina Dehner

Stefan Hubner

Jens Waschke

Affiliations

Soon will be listed here.

Abstract

Plakoglobin (Pg) and desmoplakin (DP) are adapter proteins within the desmosome, providing a mechanical link between desmosomal cadherins as transmembrane adhesion molecules and the intermediate filament cytoskeleton. As in the severe skin blistering disease pemphigus, autoantibodies against desmosomal adhesion molecules induce loss of keratinocyte cohesion at least in part via p38 mitogen-activated protein kinase (p38MAPK) activation and depletion of desmosomal components, we evaluated the roles of Pg and DP in the p38MAPK-dependent loss of cell adhesion. Silencing of either Pg or DP reduced cohesion of cultured human keratinocytes in dissociation assays. However, Pg but not DP silencing caused activation of p38MAPK-dependent keratin filament collapse and cell dissociation. Interestingly, extranuclear but not nuclear Pg rescued loss of cell adhesion and keratin retraction. In line with this, Pg regulated the levels of the desmosomal adhesion molecule desmoglein 3 and tethered p38MAPK to desmosomal complexes. Our data demonstrate a role of extranuclear Pg in controlling cell adhesion via p38MAPK-dependent regulation of keratin filament organization.

Citing Articles

Desmoplakin tail domain position in the desmosomal plaque is isoform dependent.

Ainslie C, Patel K, Tran Y, Bharathan N, Spindler V, Mattheyses A bioRxiv. 2025; .

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The impact of signaling pathways on the desmosome ultrastructure in pemphigus.

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ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology.

Simpson C, Tiwaa A, Zaver S, Johnson C, Chu E, Harms P JCI Insight. 2024; 9(21).

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Dsg3 epitope-specific signalling in pemphigus.

Schmitt T, Hudemann C, Moztarzadeh S, Hertl M, Tikkanen R, Waschke J Front Immunol. 2023; 14:1163066.

PMID: 37143675 PMC: 10151755. DOI: 10.3389/fimmu.2023.1163066.

Mechanisms Causing Acantholysis in Pemphigus-Lessons from Human Skin.

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