Desmosome dualism – most of the junction is stable, but a plakophilin moiety is persistently dynamic

Abstract

Desmosomes, strong cell-cell junctions of epithelia and cardiac muscle, link intermediate filaments to cell membranes and mechanically integrate cells across tissues, dissipating mechanical stress. They comprise five major protein classes – desmocollins and desmogleins (the desmosomal cadherins), plakoglobin, plakophilins and desmoplakin - whose individual contribution to the structure and turnover of desmosomes is poorly understood. Using live-cell imaging together with FRAP and FLAP we show that desmosomes consist of two contrasting protein moieties or modules: a very stable moiety of desmosomal cadherins, desmoplakin and plakoglobin, and a highly mobile plakophilin (Pkp2a). As desmosomes mature from calcium-dependence to calcium-independent hyper-adhesion, their stability increases, but Pkp2a remains highly mobile. We show that desmosome down-regulation during growth-factor-induced cell scattering proceeds by internalisation of whole desmosomes, which still retain a stable moiety and highly mobile Pkp2a. This molecular mobility of Pkp2a suggests a transient and probably regulatory role for Pkp2a in desmosomes.

Cortical tension regulates desmosomal morphogenesis

“…The goal of this study was to examine the influence of cortical tension on desmosomal polypeptide turnover. We focused on polypeptide components that are known to represent the stable moiety of desmosomes, i.e., desmosomal cadherins and desmoplakin ( Fulle et al, 2021 ). To make sure that the dotted structures at cell-cell borders were desmosomes, we performed double-transfection experiments of different desmosomal polypeptides.…”

“…Frontiers in Cell and Developmental Biology frontiersin.org 2003; Moch et al, 2019;Fulle et al, 2021). It is not known how this turnover is regulated and why it occurs.…”

“…They form, together with the associated keratin cytoskeleton, a transcellular scaffold, which is essential for epithelial tissue cohesion and mechanical stress dissipation. Yet, desmosomes are not just static structures but are subject to continuous turnover affecting all its components, albeit to different degrees ( Windoffer et al, 2002 ; Gloushankova et al, 2003 ; Moch et al, 2019 ; Fulle et al, 2021 ). It is not known how this turnover is regulated and why it occurs.…”

Mechanisms Causing Acantholysis in Pemphigus-Lessons from Human Skin

“…These results show that desmosome disassembly and internalization may be dependent on both cell type and stimulus. For both events, uncoupling of Dsg molecules from the cytoskeleton was shown (Figure 3D) (32,133,181,194). It remains unclear to which extent mechanical destabilization of desmosomes resulting in desmosome splitting under force results from desmosome shrinkage or keratin filament dissociation.…”

“…Recently, it was reported in Madin-Darby canine kidney (MDCK) cells that hepatocyte growth factor (HGF) induces internalization of intact desmosomes with no alteration in desmosome size and composition, which was interpreted as desmosome internalization (194). As outlined above, the situation in pemphigus is different and more complex.…”