title: Mechanosensitive components of integrin adhesions: Role of vinculin.
abstract: External forces play a key role in shaping development and normal physiology. Aberrant responses to forces, or changes in the nature of such forces, are implicated in a variety of diseases. Cells contain several types of adhesions, linking them to their external environment. It is through these adhesions that forces are both sensed (from the outside inwards) and applied (from inside to out). Furthermore, several adhesion-based proteins are sensitive to changes in intracellular forces, utilising them for activation and regulation. Here, we outline how vinculin, a key component of integrin-mediated adhesions linking the actin cytoskeleton to the extracellular matrix (ECM), is regulated by force and acts as force transducing protein. We discuss the role of vinculin in vivo and its place in health and disease; summarise the proposed mechanisms by which vinculin is recruited to and activated at integrin-ECM adhesions; and discuss recent findings that place vinculin as the major force sensing and transmitting component of cell-matrix adhesion complexes. Finally, we discuss the role of vinculin in regulating the cellular responses to both the physical properties of the external environment and to externally applied physical stimuli.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Atherton
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Stutchbury
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Devina
authors.initials: D
authors.lastname: Jethwa
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK. Electronic address: christoph.ballestrem@manchester.ac.uk.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ballestrem
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008954:Models, Biological; D013314:Stress, Mechanical; D016596:Vinculin / Q000378:metabolism*
chemical_list: D016023:Integrins; D016596:Vinculin
keywords: Actin; Focal adhesion; Force; Mechanotransduction; Vinculin