Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Joanna, Cooper, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
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
_version_ 1783345525545762816
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
work_keys_str_mv AT kimjoanna septinsregulatejunctionalintegrityofendothelialmonolayers
AT cooperjohna septinsregulatejunctionalintegrityofendothelialmonolayers