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Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity

Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that ca...

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Autores principales: Lachowicz-Scroggins, Marrah E., Gordon, Erin D., Wesolowska-Andersen, Agata, Jackson, Nathan D., MacLeod, Hannah J., Sharp, Louis Z., Sun, Matthew, Seibold, Max A., Fahy, John V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809386/
https://www.ncbi.nlm.nih.gov/pubmed/29449961
http://dx.doi.org/10.1038/s41421-017-0006-x
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author Lachowicz-Scroggins, Marrah E.
Gordon, Erin D.
Wesolowska-Andersen, Agata
Jackson, Nathan D.
MacLeod, Hannah J.
Sharp, Louis Z.
Sun, Matthew
Seibold, Max A.
Fahy, John V.
author_facet Lachowicz-Scroggins, Marrah E.
Gordon, Erin D.
Wesolowska-Andersen, Agata
Jackson, Nathan D.
MacLeod, Hannah J.
Sharp, Louis Z.
Sun, Matthew
Seibold, Max A.
Fahy, John V.
author_sort Lachowicz-Scroggins, Marrah E.
collection PubMed
description Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell–cell contact and cell integrity through maintaining cytoskeletal structures. Overexpression of CDH26 in cells with a fibroblastoid phenotype increases contact inhibition and promotes monolayer formation and cortical actin structures. CDH26 expression is also important for localization of planar cell polarity proteins. Knockdown of CDH26 in AECs results in loss of cortical actin and disruption of CRB3 and other proteins associated with apical polarity. Together, our findings uncover previously unrecognized functions for CDH26 in the maintenance of actin cytoskeleton and apicobasal polarity of AECs.
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spelling pubmed-58093862018-02-15 Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity Lachowicz-Scroggins, Marrah E. Gordon, Erin D. Wesolowska-Andersen, Agata Jackson, Nathan D. MacLeod, Hannah J. Sharp, Louis Z. Sun, Matthew Seibold, Max A. Fahy, John V. Cell Discov Article Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell–cell contact and cell integrity through maintaining cytoskeletal structures. Overexpression of CDH26 in cells with a fibroblastoid phenotype increases contact inhibition and promotes monolayer formation and cortical actin structures. CDH26 expression is also important for localization of planar cell polarity proteins. Knockdown of CDH26 in AECs results in loss of cortical actin and disruption of CRB3 and other proteins associated with apical polarity. Together, our findings uncover previously unrecognized functions for CDH26 in the maintenance of actin cytoskeleton and apicobasal polarity of AECs. Nature Publishing Group UK 2018-02-13 /pmc/articles/PMC5809386/ /pubmed/29449961 http://dx.doi.org/10.1038/s41421-017-0006-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lachowicz-Scroggins, Marrah E.
Gordon, Erin D.
Wesolowska-Andersen, Agata
Jackson, Nathan D.
MacLeod, Hannah J.
Sharp, Louis Z.
Sun, Matthew
Seibold, Max A.
Fahy, John V.
Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity
title Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity
title_full Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity
title_fullStr Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity
title_full_unstemmed Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity
title_short Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity
title_sort cadherin-26 (cdh26) regulates airway epithelial cell cytoskeletal structure and polarity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809386/
https://www.ncbi.nlm.nih.gov/pubmed/29449961
http://dx.doi.org/10.1038/s41421-017-0006-x
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