Pemphigus Foliaceus Autoantibodies Induce Redistribution Primarily of Extradesmosomal Desmoglein 1 in the Cell Membrane

Hiermaier, Matthias; Kugelmann, Daniela; Radeva, Mariya Y.; Didona, Dario; Ghoreschi, Kamran; Solimani, Farzan; Hertl, Michael; Waschke, Jens

doi:10.3389/fimmu.2022.882116

Cited by 2 publications

(1 citation statement)

References 55 publications

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“…Thus, polypeptide delivery is dependent on myosin for desmoplakin ( Godsel et al, 2005 ; Green et al, 2010 ) and dependent on kinesin-1 for desmoglein 2 and kinesin-2 for desmocollin 2, respectively ( Nekrasova et al, 2011 ). The functional importance of exchange between desmosomal and non-desmosomal pools of plasma membrane-bound desmosomal cadherins has been emphasized ( Waschke & Spindler, 2014 ; Hiermaier et al, 2022 ) and likely involves lipid rafts ( Resnik et al, 2011 ; Stahley et al, 2014 ). Endocytosis may affect individual desmosomal components ( Delva et al, 2008 ; Green et al, 2010 ; Resnik et al, 2011 ; Brennan et al, 2012 ), desmosomal halves ( Demlehner et al, 1995 ) or even entire desmosomes ( Fulle et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Cortical tension regulates desmosomal morphogenesis

Moch

Schieren

Leube

2022

Front. Cell Dev. Biol.

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Mechanical stability is a fundamental and essential property of epithelial cell sheets. It is in large part determined by cell-cell adhesion sites that are tightly integrated by the cortical cytoskeleton. An intimate crosstalk between the adherens junction-associated contractile actomyosin system and the desmosome-anchored keratin intermediate filament system is decisive for dynamic regulation of epithelial mechanics. A major question in the field is whether and in which way mechanical stress affects junctional plasticity. This is especially true for the desmosome-keratin scaffold whose role in force-sensing is virtually unknown. To examine this question, we inactivated the actomyosin system in human keratinocytes (HaCaT) and canine kidney cells (MDCK) and monitored changes in desmosomal protein turnover.Partial inhibition of myosin II by para-nitro-blebbistatin led to a decrease of the cells' elastic modulus and to reduced desmosomal protein turnover in regions where nascent desmosomes are formed and, to a lower degree, in regions where larger, more mature desmosomes are present. Interestingly, desmosomal proteins are affected differently: a significant decrease in turnover was observed for the desmosomal plaque protein desmoplakin I (DspI), which links keratin filaments to the desmosomal core, and the transmembrane cadherin desmoglein 2 (Dsg2). On the other hand, the turnover of another type of desmosomal cadherin, desmocollin 2 (Dsc2), was not significantly altered under the tested conditions. Similarly, the turnover of the adherens junction-associated E-cadherin was not affected by the low doses of para-nitro-blebbistatin. Inhibition of actin polymerization by low dose latrunculin B treatment and of ROCK-driven actomyosin contractility by Y-27632 treatment also induced a significant decrease in desmosomal DspI turnover. Taken together, we conclude that changes in the cortical force balance affect desmosome formation and growth. Furthermore, they differentially modulate desmosomal protein turnover resulting in changes of desmosome composition. We take the observations as evidence for a hitherto unknown desmosomal mechanosensing and mechanoresponse pathway responding to an altered force balance.

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