Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation
AffiliationWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
MetadataShow full item record
AbstractIntegrin 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.
CitationChastney MR, Lawless C, Humphries JD, Warwood S, Jones MC, Knight D, et al. Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation. J Cell Biol. 2020;219(8).
JournalJournal of Cell Biology
- Multiplexed Proximity Biotinylation Coupled to Mass Spectrometry for Defining Integrin Adhesion Complexes.
- Authors: Chastney MR, Lawless C, Humphries MJ
- Issue date: 2020 Sep
- Proximity-Dependent Biotinylation (BioID) of Integrin Interaction Partners.
- Authors: Myllymäki SM, Liu X, Varjosalo M, Manninen A
- Issue date: 2021
- A proteomics view on integrin-mediated adhesions.
- Authors: Manninen A, Varjosalo M
- Issue date: 2017 Feb
- Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly.
- Authors: Horton ER, Byron A, Askari JA, Ng DHJ, Millon-Frémillon A, Robertson J, Koper EJ, Paul NR, Warwood S, Knight D, Humphries JD, Humphries MJ
- Issue date: 2015 Dec
- The integrin adhesome network at a glance.
- Authors: Horton ER, Humphries JD, James J, Jones MC, Askari JA, Humphries MJ
- Issue date: 2016 Nov 15