Clustering of desmosomal cadherins by desmoplakin is essential for cell‐cell adhesion

• DOI: 10.1111/apha.13609
• Publication Date: 2020-12-24T12:09:29Z
• Authors: Marie‐Therès Wanuske; Dominique Brantschen; Camilla Schinner; Chiara Stüdle; Elias Walter; Matthias Hiermaier; Franziska Vielmuth; Jens Waschke; Volker Spindler
• Keywords: Desmosome; Plakoglobin; Desmoglein; Desmoplakin

Desmoplakin (Dp) is a crucial component of the desmosome, supramolecular cell junction complex anchoring intermediate filaments. The mechanisms how Dp modulates cell-cell adhesion are only partially understood. Here, we studied impact on function desmosomal molecules, desmosome turnover and intercellular adhesion.CRISPR/Cas9 was used for gene editing human keratinocytes which were characterized by Western blot immunostaining. Desmosomal ultrastructure assessed electron microscopy assays. Single molecule binding properties localization cadherins atomic force super-resolution imaging.Knockout (ko) impaired cohesion to drastically higher extents as ko another protein, plakoglobin (Pg). In contrast Pg ko, desmosomes completely absent in ko. Binding molecules desmocollin (Dsc) 3 desmoglein (Dsg) remained unaltered under loss Dp. required assembling into large clusters, Dsg2 Dsc3, primarily localized within desmosomes, redistributed small puncta membrane cells. Additional silencing did not further increase adhesion.Our data demonstrate that essential formation but does influence level individual cadherin properties. Rather, macro-clustering through crucial. These results may help better understand severe diseases caused dysfunction.