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Apoptotic Fragmentation of Tricellulin

Apoptotic extrusion of cells from epithelial cell layers is of central importance for epithelial homeostasis. As a prerequisite cell–cell contacts between apoptotic cells and their neighbors have to be dissociated. Tricellular tight junctions (tTJs) represent specialized structures that seal polariz...

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Autores principales: Janke, Susanne, Mittag, Sonnhild, Reiche, Juliane, Huber, Otmar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801678/
https://www.ncbi.nlm.nih.gov/pubmed/31581480
http://dx.doi.org/10.3390/ijms20194882
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author Janke, Susanne
Mittag, Sonnhild
Reiche, Juliane
Huber, Otmar
author_facet Janke, Susanne
Mittag, Sonnhild
Reiche, Juliane
Huber, Otmar
author_sort Janke, Susanne
collection PubMed
description Apoptotic extrusion of cells from epithelial cell layers is of central importance for epithelial homeostasis. As a prerequisite cell–cell contacts between apoptotic cells and their neighbors have to be dissociated. Tricellular tight junctions (tTJs) represent specialized structures that seal polarized epithelial cells at sites where three cells meet and are characterized by the specific expression of tricellulin and angulins. Here, we specifically addressed the fate of tricellulin in apoptotic cells. Methods: Apoptosis was induced by staurosporine or camptothecin in MDCKII and RT-112 cells. The fate of tricellulin was analyzed by Western blotting and immunofluorescence microscopy. Caspase activity was inhibited by Z-VAD-FMK or Z-DEVD-FMK. Results: Induction of apoptosis induces the degradation of tricellulin with time. Aspartate residues 487 and 441 were identified as caspase cleavage-sites in the C-terminal coiled-coil domain of human tricellulin. Fragmentation of tricellulin was inhibited in the presence of caspase inhibitors or when Asp487 or Asp441 were mutated to asparagine. Deletion of the tricellulin C-terminal amino acids prevented binding to lipolysis-stimulated lipoprotein receptor (LSR)/angulin-1 and thus should impair specific localization of tricellulin to tTJs. Conclusions: Tricellulin is a substrate of caspases and its cleavage in consequence contributes to the dissolution of tTJs during apoptosis.
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spelling pubmed-68016782019-10-31 Apoptotic Fragmentation of Tricellulin Janke, Susanne Mittag, Sonnhild Reiche, Juliane Huber, Otmar Int J Mol Sci Article Apoptotic extrusion of cells from epithelial cell layers is of central importance for epithelial homeostasis. As a prerequisite cell–cell contacts between apoptotic cells and their neighbors have to be dissociated. Tricellular tight junctions (tTJs) represent specialized structures that seal polarized epithelial cells at sites where three cells meet and are characterized by the specific expression of tricellulin and angulins. Here, we specifically addressed the fate of tricellulin in apoptotic cells. Methods: Apoptosis was induced by staurosporine or camptothecin in MDCKII and RT-112 cells. The fate of tricellulin was analyzed by Western blotting and immunofluorescence microscopy. Caspase activity was inhibited by Z-VAD-FMK or Z-DEVD-FMK. Results: Induction of apoptosis induces the degradation of tricellulin with time. Aspartate residues 487 and 441 were identified as caspase cleavage-sites in the C-terminal coiled-coil domain of human tricellulin. Fragmentation of tricellulin was inhibited in the presence of caspase inhibitors or when Asp487 or Asp441 were mutated to asparagine. Deletion of the tricellulin C-terminal amino acids prevented binding to lipolysis-stimulated lipoprotein receptor (LSR)/angulin-1 and thus should impair specific localization of tricellulin to tTJs. Conclusions: Tricellulin is a substrate of caspases and its cleavage in consequence contributes to the dissolution of tTJs during apoptosis. MDPI 2019-10-01 /pmc/articles/PMC6801678/ /pubmed/31581480 http://dx.doi.org/10.3390/ijms20194882 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Janke, Susanne
Mittag, Sonnhild
Reiche, Juliane
Huber, Otmar
Apoptotic Fragmentation of Tricellulin
title Apoptotic Fragmentation of Tricellulin
title_full Apoptotic Fragmentation of Tricellulin
title_fullStr Apoptotic Fragmentation of Tricellulin
title_full_unstemmed Apoptotic Fragmentation of Tricellulin
title_short Apoptotic Fragmentation of Tricellulin
title_sort apoptotic fragmentation of tricellulin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801678/
https://www.ncbi.nlm.nih.gov/pubmed/31581480
http://dx.doi.org/10.3390/ijms20194882
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