title: Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly.
abstract: Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome is likely to represent a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Horton
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.|Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Byron
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Askari
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Daniel H J
authors.initials: DHJ
authors.lastname: Ng
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Angélique
authors.initials: A
authors.lastname: Millon-Frémillon
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Ewa J
authors.initials: EJ
authors.lastname: Koper
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Nikki R
authors.initials: NR
authors.lastname: Paul
authors.affiliation: Biological Mass Spectrometry Core Facility, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Stacey
authors.initials: S
authors.lastname: Warwood
authors.affiliation: Biological Mass Spectrometry Core Facility, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Knight
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Humphries
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Humphries
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016000:Cluster Analysis; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism*; D020014:K562 Cells; D007700:Kinetics; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D015739:Nocodazole / Q000494:pharmacology; D051419:Paxillin / Q000378:metabolism; D060066:Protein Interaction Maps; D020543:Proteome / Q000145:classification / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D016608:Talin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D016596:Vinculin / Q000378:metabolism; D060589:Zyxin / Q000378:metabolism
chemical_list: D016023:Integrins; D051419:Paxillin; D020543:Proteome; D016608:Talin; D050257:Tubulin Modulators; D060589:Zyxin; D000185:Actinin; D016596:Vinculin; D015739:Nocodazole