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Adherens junctions influence tight junction formation via changes in membrane lipid composition

Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depen...

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Autores principales: Shigetomi, Kenta, Ono, Yumiko, Inai, Tetsuichiro, Ikenouchi, Junichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028530/
https://www.ncbi.nlm.nih.gov/pubmed/29720382
http://dx.doi.org/10.1083/jcb.201711042
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author Shigetomi, Kenta
Ono, Yumiko
Inai, Tetsuichiro
Ikenouchi, Junichi
author_facet Shigetomi, Kenta
Ono, Yumiko
Inai, Tetsuichiro
Ikenouchi, Junichi
author_sort Shigetomi, Kenta
collection PubMed
description Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding formation of adherens junctions (AJs) in epithelial cells; however, the underlying mechanism remains to be elucidated. In this study, loss of AJs in α-catenin–knockout (KO) EpH4 epithelial cells altered the lipid composition of the plasma membrane (PM) and led to endocytosis of claudins, a major component of TJs. Sphingomyelin with long-chain fatty acids and cholesterol were enriched in the TJ-containing PM fraction. Depletion of cholesterol abolished the formation of TJs. Conversely, addition of cholesterol restored TJ formation in α-catenin–KO cells. Collectively, we propose that AJs mediate the formation of TJs by increasing the level of cholesterol in the PM.
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spelling pubmed-60285302019-01-02 Adherens junctions influence tight junction formation via changes in membrane lipid composition Shigetomi, Kenta Ono, Yumiko Inai, Tetsuichiro Ikenouchi, Junichi J Cell Biol Research Articles Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding formation of adherens junctions (AJs) in epithelial cells; however, the underlying mechanism remains to be elucidated. In this study, loss of AJs in α-catenin–knockout (KO) EpH4 epithelial cells altered the lipid composition of the plasma membrane (PM) and led to endocytosis of claudins, a major component of TJs. Sphingomyelin with long-chain fatty acids and cholesterol were enriched in the TJ-containing PM fraction. Depletion of cholesterol abolished the formation of TJs. Conversely, addition of cholesterol restored TJ formation in α-catenin–KO cells. Collectively, we propose that AJs mediate the formation of TJs by increasing the level of cholesterol in the PM. Rockefeller University Press 2018-07-02 /pmc/articles/PMC6028530/ /pubmed/29720382 http://dx.doi.org/10.1083/jcb.201711042 Text en © 2018 Shigetomi et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Shigetomi, Kenta
Ono, Yumiko
Inai, Tetsuichiro
Ikenouchi, Junichi
Adherens junctions influence tight junction formation via changes in membrane lipid composition
title Adherens junctions influence tight junction formation via changes in membrane lipid composition
title_full Adherens junctions influence tight junction formation via changes in membrane lipid composition
title_fullStr Adherens junctions influence tight junction formation via changes in membrane lipid composition
title_full_unstemmed Adherens junctions influence tight junction formation via changes in membrane lipid composition
title_short Adherens junctions influence tight junction formation via changes in membrane lipid composition
title_sort adherens junctions influence tight junction formation via changes in membrane lipid composition
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028530/
https://www.ncbi.nlm.nih.gov/pubmed/29720382
http://dx.doi.org/10.1083/jcb.201711042
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