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PLEKHA7 modulates epithelial tight junction barrier function

PLEKHA7 is a recently identified protein of the epithelial zonula adhaerens (ZA), and is part of a protein complex that stabilizes the ZA, by linking it to microtubules. Since the ZA is important in the assembly and disassembly of tight junctions (TJ), we asked whether PLEKHA7 is involved in modulat...

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Autores principales: Paschoud, Serge, Jond, Lionel, Guerrera, Diego, Citi, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022608/
https://www.ncbi.nlm.nih.gov/pubmed/24843844
http://dx.doi.org/10.4161/tisb.28755
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author Paschoud, Serge
Jond, Lionel
Guerrera, Diego
Citi, Sandra
author_facet Paschoud, Serge
Jond, Lionel
Guerrera, Diego
Citi, Sandra
author_sort Paschoud, Serge
collection PubMed
description PLEKHA7 is a recently identified protein of the epithelial zonula adhaerens (ZA), and is part of a protein complex that stabilizes the ZA, by linking it to microtubules. Since the ZA is important in the assembly and disassembly of tight junctions (TJ), we asked whether PLEKHA7 is involved in modulating epithelial TJ barrier function. We generated clonal MDCK cell lines in which one of four different constructs of PLEKHA7 was inducibly expressed. All constructs were localized at junctions, but constructs lacking the C-terminal region were also distributed diffusely in the cytoplasm. Inducible expression of PLEKHA7 constructs did not affect the expression and localization of TJ proteins, the steady-state value of transepithelial resistance (TER), the development of TER during the calcium switch, and the flux of large molecules across confluent monolayers. In contrast, expression of three out of four constructs resulted both in enhanced recruitment of E-cadherin and associated proteins at the apical ZA and at lateral puncta adherentia (PA), a decreased TER at 18 h after assembly at normal calcium, and an attenuation in the fall in TER after extracellular calcium removal. This latter effect was inhibited when cells were treated with nocodazole. Immunoprecipitation analysis showed that PLEKHA7 forms a complex with the cytoplasmic TJ proteins ZO-1 and cingulin, and this association does not depend on the integrity of microtubules. These results suggest that PLEKHA7 modulates the dynamics of assembly and disassembly of the TJ barrier, through E-cadherin protein complex- and microtubule-dependent mechanisms.
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spelling pubmed-40226082014-05-19 PLEKHA7 modulates epithelial tight junction barrier function Paschoud, Serge Jond, Lionel Guerrera, Diego Citi, Sandra Tissue Barriers Research Paper PLEKHA7 is a recently identified protein of the epithelial zonula adhaerens (ZA), and is part of a protein complex that stabilizes the ZA, by linking it to microtubules. Since the ZA is important in the assembly and disassembly of tight junctions (TJ), we asked whether PLEKHA7 is involved in modulating epithelial TJ barrier function. We generated clonal MDCK cell lines in which one of four different constructs of PLEKHA7 was inducibly expressed. All constructs were localized at junctions, but constructs lacking the C-terminal region were also distributed diffusely in the cytoplasm. Inducible expression of PLEKHA7 constructs did not affect the expression and localization of TJ proteins, the steady-state value of transepithelial resistance (TER), the development of TER during the calcium switch, and the flux of large molecules across confluent monolayers. In contrast, expression of three out of four constructs resulted both in enhanced recruitment of E-cadherin and associated proteins at the apical ZA and at lateral puncta adherentia (PA), a decreased TER at 18 h after assembly at normal calcium, and an attenuation in the fall in TER after extracellular calcium removal. This latter effect was inhibited when cells were treated with nocodazole. Immunoprecipitation analysis showed that PLEKHA7 forms a complex with the cytoplasmic TJ proteins ZO-1 and cingulin, and this association does not depend on the integrity of microtubules. These results suggest that PLEKHA7 modulates the dynamics of assembly and disassembly of the TJ barrier, through E-cadherin protein complex- and microtubule-dependent mechanisms. Landes Bioscience 2014-04-02 /pmc/articles/PMC4022608/ /pubmed/24843844 http://dx.doi.org/10.4161/tisb.28755 Text en Copyright © 2014 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Research Paper
Paschoud, Serge
Jond, Lionel
Guerrera, Diego
Citi, Sandra
PLEKHA7 modulates epithelial tight junction barrier function
title PLEKHA7 modulates epithelial tight junction barrier function
title_full PLEKHA7 modulates epithelial tight junction barrier function
title_fullStr PLEKHA7 modulates epithelial tight junction barrier function
title_full_unstemmed PLEKHA7 modulates epithelial tight junction barrier function
title_short PLEKHA7 modulates epithelial tight junction barrier function
title_sort plekha7 modulates epithelial tight junction barrier function
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022608/
https://www.ncbi.nlm.nih.gov/pubmed/24843844
http://dx.doi.org/10.4161/tisb.28755
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