Biology subjects

Stüdle, C.

Publications and source records attributed to Stüdle, C..

3 recordsLinked to original sources

bioRxiv2022

Desmosomal cell cohesion and epidermal differentiation are modulated by dolichol phosphate mannosyltransferase 1 (DPM1) through SERPINB5-dependent mechanisms

Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, for desmosomal adhesive function and epidermal differentiation. Deletion of the key molecule of the DPM complex, DPM1, in human keratinocytes resulted in weakened cell-cell adhesion, impaired localization of the desmosomal components desmoplakin and desmoglein-2, and led to cytoskeletal organization defects in human keratinocytes. In a 3D organotypic human epidermis model, loss of DPM1 caused impaired differentiation with abnormally increased cornification, reduced thickness of non-corneal layers, and formation of intercellular gaps in the epidermis. Using proteomic approaches, SERPINB5 was identified as DPM1-dependent interaction partner of desmoplakin. Mechanistically, SERPINB5 reduced desmoplakin phosphorylation at serine 176, which was required for strong intercellular adhesion. These results uncover a novel role of the DPM complex in linking desmosomal adhesion with epidermal differentiation.

cell biology↗

bioRxiv2020

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

Desmoplakin (Dp) localizes to desmosomes, linking clusters of desmosomal adhesion molecules to the intermediate filament cytoskeleton. Here, we generated Dp knockout (ko) cell lines of human keratinocytes to study the impact on desmosomal adhesion molecules and desmosome turnover using atomic force microscopy and superresolution imaging. In comparison to ko of another desmosomal component, plakoglobin (Pg), loss of Dp resulted in absence of desmosomes and drastically impaired cell cohesion. In Dp ko, the desmosomal adhesion molecules desmoglein 2 (Dsg2) and desmocollin 3 (Dsc3) were redistributed into small clusters in the cell membrane with no further increase in loss of intercellular adhesion by silencing of Dsg2. This suggests that extradesmosomal cadherins do not significantly contribute to cell cohesion but rather localization within desmosomes is required. Our data outline a crucial role of Dp for both desmosomal molecule clustering and mature desmosome formation and provide novel insights into the regulation of intercellular adhesion.

cell biology↗

bioRxiv2019

The actin binding protein α-adducin modulates desmosomal turnover and plasticity

Intercellular adhesion is essential for tissue integrity and homeostasis. Desmosomes are especially abundant in the epidermis and the myocardium, tissues, which are under constantly changing mechanical stresses. Yet, it is largely unclear whether desmosomal adhesion can be rapidly adapted to changing demands and the mechanisms underlying desmosome turnover are only partially understood. We here show that loss of the actin-binding protein -adducin prevented the ability of cultured keratinocytes or murine epidermis to withstand mechanical stress paralleled with reduced desmosome number. This effect was not caused by decreased levels or impaired adhesive properties of desmosomal molecules but rather by altered desmosome turnover. Mechanistically, reduced cortical actin density in -adducin knockout keratinocytes resulted in increased mobility of the desmosomal adhesion molecule desmoglein 3 (Dsg3) and impaired interactions with E-cadherin, a crucial step in desmosome formation. Accordingly, loss of -adducin prevented increased membrane localization of Dsg3 in response to cyclic stretch or shear stress. Our data demonstrate plasticity of desmosomal molecules in response to mechanical stimuli and unravel a mechanism how the actin cytoskeleton indirectly shapes intercellular adhesion by restricting the mobility of desmosomal molecules.

cell biology↗