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Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions
Integrins are the core constituents of cell–matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987715/ https://www.ncbi.nlm.nih.gov/pubmed/29632027 http://dx.doi.org/10.1083/jcb.201707075 |
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author | Spiess, Matthias Hernandez-Varas, Pablo Oddone, Anna Olofsson, Helene Blom, Hans Waithe, Dominic Lock, John G. Lakadamyali, Melike Strömblad, Staffan |
author_facet | Spiess, Matthias Hernandez-Varas, Pablo Oddone, Anna Olofsson, Helene Blom, Hans Waithe, Dominic Lock, John G. Lakadamyali, Melike Strömblad, Staffan |
author_sort | Spiess, Matthias |
collection | PubMed |
description | Integrins are the core constituents of cell–matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive β1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive β1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation. |
format | Online Article Text |
id | pubmed-5987715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59877152018-12-04 Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions Spiess, Matthias Hernandez-Varas, Pablo Oddone, Anna Olofsson, Helene Blom, Hans Waithe, Dominic Lock, John G. Lakadamyali, Melike Strömblad, Staffan J Cell Biol Research Articles Integrins are the core constituents of cell–matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive β1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive β1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation. Rockefeller University Press 2018-06-04 /pmc/articles/PMC5987715/ /pubmed/29632027 http://dx.doi.org/10.1083/jcb.201707075 Text en © 2018 Spiess et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Spiess, Matthias Hernandez-Varas, Pablo Oddone, Anna Olofsson, Helene Blom, Hans Waithe, Dominic Lock, John G. Lakadamyali, Melike Strömblad, Staffan Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
title | Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
title_full | Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
title_fullStr | Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
title_full_unstemmed | Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
title_short | Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
title_sort | active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987715/ https://www.ncbi.nlm.nih.gov/pubmed/29632027 http://dx.doi.org/10.1083/jcb.201707075 |
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