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Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation

Maintenance of epithelial cell adhesion is crucial for epidermal morphogenesis and homeostasis and relies predominantly on the interaction of keratins with desmosomes. Although the importance of desmosomes to epidermal coherence and keratin organization is well established, the significance of kerat...

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Autores principales: Kröger, Cornelia, Loschke, Fanny, Schwarz, Nicole, Windoffer, Reinhard, Leube, Rudolf E., Magin, Thomas M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664716/
https://www.ncbi.nlm.nih.gov/pubmed/23690176
http://dx.doi.org/10.1083/jcb.201208162
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author Kröger, Cornelia
Loschke, Fanny
Schwarz, Nicole
Windoffer, Reinhard
Leube, Rudolf E.
Magin, Thomas M.
author_facet Kröger, Cornelia
Loschke, Fanny
Schwarz, Nicole
Windoffer, Reinhard
Leube, Rudolf E.
Magin, Thomas M.
author_sort Kröger, Cornelia
collection PubMed
description Maintenance of epithelial cell adhesion is crucial for epidermal morphogenesis and homeostasis and relies predominantly on the interaction of keratins with desmosomes. Although the importance of desmosomes to epidermal coherence and keratin organization is well established, the significance of keratins in desmosome organization has not been fully resolved. Here, we report that keratinocytes lacking all keratins show elevated, PKC-α–mediated desmoplakin phosphorylation and subsequent destabilization of desmosomes. We find that PKC-α activity is regulated by Rack1–keratin interaction. Without keratins, desmosomes assemble but are endocytosed at accelerated rates, rendering epithelial sheets highly susceptible to mechanical stress. Re-expression of the keratin pair K5/14, inhibition of PKC-α activity, or blocking of endocytosis reconstituted both desmosome localization at the plasma membrane and epithelial adhesion. Our findings identify a hitherto unknown mechanism by which keratins control intercellular adhesion, with potential implications for tumor invasion and keratinopathies, settings in which diminished cell adhesion facilitates tissue fragility and neoplastic growth.
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spelling pubmed-36647162013-11-27 Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation Kröger, Cornelia Loschke, Fanny Schwarz, Nicole Windoffer, Reinhard Leube, Rudolf E. Magin, Thomas M. J Cell Biol Research Articles Maintenance of epithelial cell adhesion is crucial for epidermal morphogenesis and homeostasis and relies predominantly on the interaction of keratins with desmosomes. Although the importance of desmosomes to epidermal coherence and keratin organization is well established, the significance of keratins in desmosome organization has not been fully resolved. Here, we report that keratinocytes lacking all keratins show elevated, PKC-α–mediated desmoplakin phosphorylation and subsequent destabilization of desmosomes. We find that PKC-α activity is regulated by Rack1–keratin interaction. Without keratins, desmosomes assemble but are endocytosed at accelerated rates, rendering epithelial sheets highly susceptible to mechanical stress. Re-expression of the keratin pair K5/14, inhibition of PKC-α activity, or blocking of endocytosis reconstituted both desmosome localization at the plasma membrane and epithelial adhesion. Our findings identify a hitherto unknown mechanism by which keratins control intercellular adhesion, with potential implications for tumor invasion and keratinopathies, settings in which diminished cell adhesion facilitates tissue fragility and neoplastic growth. The Rockefeller University Press 2013-05-27 /pmc/articles/PMC3664716/ /pubmed/23690176 http://dx.doi.org/10.1083/jcb.201208162 Text en © 2013 Kröger et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Kröger, Cornelia
Loschke, Fanny
Schwarz, Nicole
Windoffer, Reinhard
Leube, Rudolf E.
Magin, Thomas M.
Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation
title Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation
title_full Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation
title_fullStr Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation
title_full_unstemmed Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation
title_short Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation
title_sort keratins control intercellular adhesion involving pkc-α–mediated desmoplakin phosphorylation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664716/
https://www.ncbi.nlm.nih.gov/pubmed/23690176
http://dx.doi.org/10.1083/jcb.201208162
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