title: Mechanosensitivity of integrin adhesion complexes: role of the consensus adhesome.
abstract: Cell and tissue stiffness have been known to contribute to both developmental and pathological signalling for some time, but the underlying mechanisms remain elusive. Integrins and their associated adhesion signalling complexes (IACs), which form a nexus between the cell cytoskeleton and the extracellular matrix, act as a key force sensing and transducing unit in cells. Accordingly, there has been much interest in obtaining a systems-level understanding of IAC composition. Proteomic approaches have revealed the complexity of IACs and identified a large number of components that are regulated by cytoskeletal force. Here we review the function of the consensus adhesome, an assembly of core IAC proteins that emerged from a meta-analysis of multiple proteomic datasets, in the context of mechanosensing. As IAC components have been linked to a variety of diseases involved with rigidity sensing, the field is now in a position to define the mechanosensing function of individual IAC proteins and elucidate their mechanisms of action.
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.
authors.forename: Pablo
authors.initials: P
authors.lastname: Astudillo
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: martin.humphries@manchester.ac.uk.
authors.forename: Martin J
authors.initials: MJ
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: Jonathan D
authors.initials: JD
authors.lastname: Humphries
mesh_terms: D056831:Coordination Complexes; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D040901:Proteomics; D013314:Stress, Mechanical
chemical_list: D056831:Coordination Complexes; D016023:Integrins
keywords: Cell adhesion; Consensus adhesome; Extracellular matrix; Focal adhesions; Integrins; Mass spectrometry-based proteomics; Mechanosensing