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-...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/63253 |
| _version_ | 1811180670426284032 |
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| author | Esther Sasson Shira Anzi Batia Bell Oren Yakovian Meshi Zorsky Urban Deutsch Britta Engelhardt Eilon Sherman Gad Vatine Ron Dzikowski Ayal Ben-Zvi |
| author_facet | Esther Sasson Shira Anzi Batia Bell Oren Yakovian Meshi Zorsky Urban Deutsch Britta Engelhardt Eilon Sherman Gad Vatine Ron Dzikowski Ayal Ben-Zvi |
| author_sort | Esther Sasson |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T09:06:59Z |
| format | Article |
| id | doaj.art-477a0873a85743b4957c023d577a0991 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:59Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-477a0873a85743b4957c023d577a09912022-12-22T04:32:36ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.63253Nano-scale architecture of blood-brain barrier tight-junctionsEsther Sasson0https://orcid.org/0000-0001-7156-1516Shira Anzi1Batia Bell2Oren Yakovian3Meshi Zorsky4Urban Deutsch5Britta Engelhardt6Eilon Sherman7Gad Vatine8Ron Dzikowski9Ayal Ben-Zvi10https://orcid.org/0000-0003-4012-7789Department of Developmental Biology and Cancer Research, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Hebrew University of Jerusalem, Jerusalem, IsraelRacah Institute of Physics, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, IsraelTheodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandRacah Institute of Physics, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, IsraelDepartment of Microbiology and Molecular Genetics, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Hebrew University of Jerusalem, Jerusalem, IsraelTight 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.https://elifesciences.org/articles/63253blood-brain-barriertight-junctionsuper-resolutionendothelium |
| spellingShingle | Esther Sasson Shira Anzi Batia Bell Oren Yakovian Meshi Zorsky Urban Deutsch Britta Engelhardt Eilon Sherman Gad Vatine Ron Dzikowski Ayal Ben-Zvi Nano-scale architecture of blood-brain barrier tight-junctions eLife blood-brain-barrier tight-junction super-resolution endothelium |
| 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 | blood-brain-barrier tight-junction super-resolution endothelium |
| url | https://elifesciences.org/articles/63253 |
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