Extracellular Redox Regulation of α7β Integrin-Mediated Cell Migration Is Signaled via a Dominant Thiol-Switch.

ABSTRACT: While adhering to extracellular matrix (ECM) proteins, such as laminin-111, cells temporarily produce hydrogen peroxide at adhesion sites. To study the redox regulation of α7β1 integrin-mediated cell adhesion to laminin-111, a conserved cysteine pair within the α-subunit hinge region was replaced for alanines. The molecular and cellular effects were analyzed by electron and atomic force microscopy, impedance-based migration assays, flow cytometry and live cell imaging. This cysteine pair constitutes a thiol-switch, which redox-dependently governs the equilibrium between an extended and a bent integrin conformation with high and low ligand binding activity, respectively. Hydrogen peroxide oxidizes the cysteines to a disulfide bond, increases ligand binding and promotes cell migration toward

SUBMITTER: Bergerhausen L 

PROVIDER: S-EPMC7139957 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature