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Septins regulate junctional integrity of endothelial monolayers
Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, w...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080707/ https://www.ncbi.nlm.nih.gov/pubmed/29771630 http://dx.doi.org/10.1091/mbc.E18-02-0136 |
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author | Kim, Joanna Cooper, John A. |
author_facet | Kim, Joanna Cooper, John A. |
author_sort | Kim, Joanna |
collection | PubMed |
description | Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions extending above or below neighboring cells. Vascular endothelial cadherin (VE-cadherin) was present at cell junctions, with a membrane-associated layer of F-actin. Septins localized at cell-junction membranes, in patterns distinct from VE-cadherin and F-actin. Septins assumed curved and scallop-shaped patterns at junctions, especially in regions of positive membrane curvature associated with actin-rich membrane protrusions. Depletion of septins led to disrupted morphology of VE-cadherin junctions and increased expression of VE-cadherin. In videos, septin-depleted cells displayed remodeling at cell junctions; regions with VE-cadherin were broader, and areas with membrane ruffling were wider. Septin depletion and junction disruption led to functional loss of junctional integrity, revealed by decreased transendothelial electric resistance and increased transmigration of immune cells. We conclude that septins, as cytoskeletal elements associated with the plasma membrane, are important for cell junctions and junctional integrity of endothelial monolayers, functioning at regions of positive curvature in support of actin-rich protrusions to promote cadherin-based cell junctions. |
format | Online Article Text |
id | pubmed-6080707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-60807072018-09-30 Septins regulate junctional integrity of endothelial monolayers Kim, Joanna Cooper, John A. Mol Biol Cell Articles Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions extending above or below neighboring cells. Vascular endothelial cadherin (VE-cadherin) was present at cell junctions, with a membrane-associated layer of F-actin. Septins localized at cell-junction membranes, in patterns distinct from VE-cadherin and F-actin. Septins assumed curved and scallop-shaped patterns at junctions, especially in regions of positive membrane curvature associated with actin-rich membrane protrusions. Depletion of septins led to disrupted morphology of VE-cadherin junctions and increased expression of VE-cadherin. In videos, septin-depleted cells displayed remodeling at cell junctions; regions with VE-cadherin were broader, and areas with membrane ruffling were wider. Septin depletion and junction disruption led to functional loss of junctional integrity, revealed by decreased transendothelial electric resistance and increased transmigration of immune cells. We conclude that septins, as cytoskeletal elements associated with the plasma membrane, are important for cell junctions and junctional integrity of endothelial monolayers, functioning at regions of positive curvature in support of actin-rich protrusions to promote cadherin-based cell junctions. The American Society for Cell Biology 2018-07-15 /pmc/articles/PMC6080707/ /pubmed/29771630 http://dx.doi.org/10.1091/mbc.E18-02-0136 Text en © 2018 Kim and Cooper. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Kim, Joanna Cooper, John A. Septins regulate junctional integrity of endothelial monolayers |
title | Septins regulate junctional integrity of endothelial monolayers |
title_full | Septins regulate junctional integrity of endothelial monolayers |
title_fullStr | Septins regulate junctional integrity of endothelial monolayers |
title_full_unstemmed | Septins regulate junctional integrity of endothelial monolayers |
title_short | Septins regulate junctional integrity of endothelial monolayers |
title_sort | septins regulate junctional integrity of endothelial monolayers |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080707/ https://www.ncbi.nlm.nih.gov/pubmed/29771630 http://dx.doi.org/10.1091/mbc.E18-02-0136 |
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