Cargando…
Occludin is required for apoptosis when claudin–claudin interactions are disrupted
Disruption of tight junctions is often seen during pathogen infection, inflammation, and tumor progression. Mislocalization of the tight junction proteins occludin and claudin in mammary epithelial monolayers leads to apoptosis through the extrinsic pathway. To further investigate the mechanism of t...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288343/ https://www.ncbi.nlm.nih.gov/pubmed/22361748 http://dx.doi.org/10.1038/cddis.2012.14 |
_version_ | 1782224811843387392 |
---|---|
author | Beeman, N Webb, P G Baumgartner, H K |
author_facet | Beeman, N Webb, P G Baumgartner, H K |
author_sort | Beeman, N |
collection | PubMed |
description | Disruption of tight junctions is often seen during pathogen infection, inflammation, and tumor progression. Mislocalization of the tight junction proteins occludin and claudin in mammary epithelial monolayers leads to apoptosis through the extrinsic pathway. To further investigate the mechanism of this response, a normal mammary epithelial cell line (EpH4) as well as primary mammary epithelial cells were treated with a claudin-disrupting mimic peptide, DFYNP (aspartic acid–phenylalanine–tyrosine–asparagine–proline). Using fluorescent indicators, we found that caspase-3 activation, resulting from treatment with DFYNP, was restricted to EpH4 and primary mammary epithelial cells with mislocalized claudin-4. Mislocalized claudin-4 and occludin were colocalized in non-junctional puncta, and both molecules were found in the death-inducing signaling complex (DISC) where they colocalized with Fas, fas-associated protein with death domain (FADD), active caspase-8 and caspase-3 at distinct apical domains. Importantly, caspase-3 activation was totally repressed in primary mammary epithelial cells from occludin null mice. Thus, the apoptotic response appears to be initiated by the movement of occludin to the DISC suggesting that this molecule has signaling properties that initiate cell death when its tight junction location is disrupted. |
format | Online Article Text |
id | pubmed-3288343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-32883432012-02-28 Occludin is required for apoptosis when claudin–claudin interactions are disrupted Beeman, N Webb, P G Baumgartner, H K Cell Death Dis Original Article Disruption of tight junctions is often seen during pathogen infection, inflammation, and tumor progression. Mislocalization of the tight junction proteins occludin and claudin in mammary epithelial monolayers leads to apoptosis through the extrinsic pathway. To further investigate the mechanism of this response, a normal mammary epithelial cell line (EpH4) as well as primary mammary epithelial cells were treated with a claudin-disrupting mimic peptide, DFYNP (aspartic acid–phenylalanine–tyrosine–asparagine–proline). Using fluorescent indicators, we found that caspase-3 activation, resulting from treatment with DFYNP, was restricted to EpH4 and primary mammary epithelial cells with mislocalized claudin-4. Mislocalized claudin-4 and occludin were colocalized in non-junctional puncta, and both molecules were found in the death-inducing signaling complex (DISC) where they colocalized with Fas, fas-associated protein with death domain (FADD), active caspase-8 and caspase-3 at distinct apical domains. Importantly, caspase-3 activation was totally repressed in primary mammary epithelial cells from occludin null mice. Thus, the apoptotic response appears to be initiated by the movement of occludin to the DISC suggesting that this molecule has signaling properties that initiate cell death when its tight junction location is disrupted. Nature Publishing Group 2012-02 2012-02-23 /pmc/articles/PMC3288343/ /pubmed/22361748 http://dx.doi.org/10.1038/cddis.2012.14 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Beeman, N Webb, P G Baumgartner, H K Occludin is required for apoptosis when claudin–claudin interactions are disrupted |
title | Occludin is required for apoptosis when claudin–claudin interactions are disrupted |
title_full | Occludin is required for apoptosis when claudin–claudin interactions are disrupted |
title_fullStr | Occludin is required for apoptosis when claudin–claudin interactions are disrupted |
title_full_unstemmed | Occludin is required for apoptosis when claudin–claudin interactions are disrupted |
title_short | Occludin is required for apoptosis when claudin–claudin interactions are disrupted |
title_sort | occludin is required for apoptosis when claudin–claudin interactions are disrupted |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288343/ https://www.ncbi.nlm.nih.gov/pubmed/22361748 http://dx.doi.org/10.1038/cddis.2012.14 |
work_keys_str_mv | AT beemann occludinisrequiredforapoptosiswhenclaudinclaudininteractionsaredisrupted AT webbpg occludinisrequiredforapoptosiswhenclaudinclaudininteractionsaredisrupted AT baumgartnerhk occludinisrequiredforapoptosiswhenclaudinclaudininteractionsaredisrupted |