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Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation
Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry, and topological organization of proteins within IACs are not fully understood. To address...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401799/ https://www.ncbi.nlm.nih.gov/pubmed/32585685 http://dx.doi.org/10.1083/jcb.202003038 |
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author | Chastney, Megan R. Lawless, Craig Humphries, Jonathan D. Warwood, Stacey Jones, Matthew C. Knight, David Jorgensen, Claus Humphries, Martin J. |
author_facet | Chastney, Megan R. Lawless, Craig Humphries, Jonathan D. Warwood, Stacey Jones, Matthew C. Knight, David Jorgensen, Claus Humphries, Martin J. |
author_sort | Chastney, Megan R. |
collection | PubMed |
description | Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry, and topological organization of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level. |
format | Online Article Text |
id | pubmed-7401799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74017992021-02-03 Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation Chastney, Megan R. Lawless, Craig Humphries, Jonathan D. Warwood, Stacey Jones, Matthew C. Knight, David Jorgensen, Claus Humphries, Martin J. J Cell Biol Tools Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry, and topological organization of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level. Rockefeller University Press 2020-06-25 /pmc/articles/PMC7401799/ /pubmed/32585685 http://dx.doi.org/10.1083/jcb.202003038 Text en © 2020 Chastney 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 | Tools Chastney, Megan R. Lawless, Craig Humphries, Jonathan D. Warwood, Stacey Jones, Matthew C. Knight, David Jorgensen, Claus Humphries, Martin J. Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
title | Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
title_full | Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
title_fullStr | Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
title_full_unstemmed | Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
title_short | Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
title_sort | topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation |
topic | Tools |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401799/ https://www.ncbi.nlm.nih.gov/pubmed/32585685 http://dx.doi.org/10.1083/jcb.202003038 |
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