Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Spiess, Matthias, Hernandez-Varas, Pablo, Oddone, Anna, Olofsson, Helene, Blom, Hans, Waithe, Dominic, Lock, John G., Lakadamyali, Melike, Strömblad, Staffan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
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
_version_ 1783329174906208256
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
work_keys_str_mv AT spiessmatthias activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT hernandezvaraspablo activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT oddoneanna activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT olofssonhelene activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT blomhans activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT waithedominic activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT lockjohng activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT lakadamyalimelike activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions
AT strombladstaffan activeandinactiveb1integrinssegregateintodistinctnanoclustersinfocaladhesions