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Nano-scale architecture of blood-brain barrier tight-junctions
Tight junctions (TJs) between blood-brain barrier (BBB) endothelial cells construct a robust physical barrier, whose damage underlies BBB dysfunctions related to several neurodegenerative diseases. What makes these highly specialized BBB-TJs extremely restrictive remains unknown. Here, we use super-...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747500/ https://www.ncbi.nlm.nih.gov/pubmed/34951586 http://dx.doi.org/10.7554/eLife.63253 |
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author | Sasson, Esther Anzi, Shira Bell, Batia Yakovian, Oren Zorsky, Meshi Deutsch, Urban Engelhardt, Britta Sherman, Eilon Vatine, Gad Dzikowski, Ron Ben-Zvi, Ayal |
author_facet | Sasson, Esther Anzi, Shira Bell, Batia Yakovian, Oren Zorsky, Meshi Deutsch, Urban Engelhardt, Britta Sherman, Eilon Vatine, Gad Dzikowski, Ron Ben-Zvi, Ayal |
author_sort | Sasson, Esther |
collection | PubMed |
description | Tight junctions (TJs) between blood-brain barrier (BBB) endothelial cells construct a robust physical barrier, whose damage underlies BBB dysfunctions related to several neurodegenerative diseases. What makes these highly specialized BBB-TJs extremely restrictive remains unknown. Here, we use super-resolution microscopy (dSTORM) to uncover new structural and functional properties of BBB TJs. Focusing on three major components, Nano-scale resolution revealed sparse (occludin) vs. clustered (ZO1/claudin-5) molecular architecture. In mouse development, permeable TJs become first restrictive to large molecules, and only later to small molecules, with claudin-5 proteins arrangement compacting during this maturation process. Mechanistically, we reveal that ZO1 clustering is independent of claudin-5 in vivo. In contrast to accepted knowledge, we found that in the developmental context, total levels of claudin-5 inversely correlate with TJ functionality. Our super-resolution studies provide a unique perspective of BBB TJs and open new directions for understanding TJ functionality in biological barriers, ultimately enabling restoration in disease or modulation for drug delivery. |
format | Online Article Text |
id | pubmed-8747500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-87475002022-01-12 Nano-scale architecture of blood-brain barrier tight-junctions Sasson, Esther Anzi, Shira Bell, Batia Yakovian, Oren Zorsky, Meshi Deutsch, Urban Engelhardt, Britta Sherman, Eilon Vatine, Gad Dzikowski, Ron Ben-Zvi, Ayal eLife Cell Biology Tight junctions (TJs) between blood-brain barrier (BBB) endothelial cells construct a robust physical barrier, whose damage underlies BBB dysfunctions related to several neurodegenerative diseases. What makes these highly specialized BBB-TJs extremely restrictive remains unknown. Here, we use super-resolution microscopy (dSTORM) to uncover new structural and functional properties of BBB TJs. Focusing on three major components, Nano-scale resolution revealed sparse (occludin) vs. clustered (ZO1/claudin-5) molecular architecture. In mouse development, permeable TJs become first restrictive to large molecules, and only later to small molecules, with claudin-5 proteins arrangement compacting during this maturation process. Mechanistically, we reveal that ZO1 clustering is independent of claudin-5 in vivo. In contrast to accepted knowledge, we found that in the developmental context, total levels of claudin-5 inversely correlate with TJ functionality. Our super-resolution studies provide a unique perspective of BBB TJs and open new directions for understanding TJ functionality in biological barriers, ultimately enabling restoration in disease or modulation for drug delivery. eLife Sciences Publications, Ltd 2021-12-24 /pmc/articles/PMC8747500/ /pubmed/34951586 http://dx.doi.org/10.7554/eLife.63253 Text en © 2021, Sasson et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Sasson, Esther Anzi, Shira Bell, Batia Yakovian, Oren Zorsky, Meshi Deutsch, Urban Engelhardt, Britta Sherman, Eilon Vatine, Gad Dzikowski, Ron Ben-Zvi, Ayal Nano-scale architecture of blood-brain barrier tight-junctions |
title | Nano-scale architecture of blood-brain barrier tight-junctions |
title_full | Nano-scale architecture of blood-brain barrier tight-junctions |
title_fullStr | Nano-scale architecture of blood-brain barrier tight-junctions |
title_full_unstemmed | Nano-scale architecture of blood-brain barrier tight-junctions |
title_short | Nano-scale architecture of blood-brain barrier tight-junctions |
title_sort | nano-scale architecture of blood-brain barrier tight-junctions |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747500/ https://www.ncbi.nlm.nih.gov/pubmed/34951586 http://dx.doi.org/10.7554/eLife.63253 |
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