Dataset Information

Extracellular Redox Regulation of ?7? 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 ?7?1 integrin-mediated cell adhesion to laminin-111, a conserved cysteine pair within the ?-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 laminin-111. Inversely, extracellular thioredoxin-1 reduces the disulfide, thereby decreasing laminin binding. Mutation of this cysteine pair into the non-oxidizable hinge-mutant shows molecular and cellular effects similar to the reduced wild-type integrin, but lacks redox regulation. This proves the existence of a dominant thiol-switch within the ? subunit hinge of ?7?1 integrin, which is sufficient to implement activity regulation by extracellular redox agents in a redox-regulatory circuit. Our data reveal a novel and physiologically relevant thiol-based regulatory mechanism of integrin-mediated cell-ECM interactions, which employs short-lived hydrogen peroxide and extracellular thioredoxin-1 as signaling mediators.

SUBMITTER: Bergerhausen L

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

REPOSITORIES: biostudies-literature

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

Bergerhausen Lukas L Grosche Julius J Meißner Juliane J Hecker Christina C Caliandro Michele F MF Westerhausen Christoph C Kamenac Andrej A Rezaei Maryam M Mörgelin Matthias M Poschmann Gereon G Vestweber Dietmar D Hanschmann Eva-Maria EM Eble Johannes A JA

Antioxidants (Basel, Switzerland) 20200310 3

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 constit ...[more]

PMID: 32164274

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Dataset Information

Extracellular Redox Regulation of ?7? Integrin-Mediated Cell Migration Is Signaled via a Dominant Thiol-Switch.

Publications

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

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