The role of Protein Disulfide Isomerase and thiol bonds modifications in activation of integrin subunit alpha11

• Published in: Biochemical and biophysical research communications 2018-01, Vol.495 (2), p.1635-1641
• Main Authors: Popielarski, Marcin, Ponamarczuk, Halszka, Stasiak, Marta, Michalec, Lidia, Bednarek, Radoslaw, Studzian, Maciej, Pulaski, Lukasz, Swiatkowska, Maria
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; CYSTEINE; Disulfide bonds; DISULFIDES; Integrin alpha11; ISOMERASES; Oxidation-reduction reactions; Protein Disulfide Isomerase; RECEPTORS; REDOX REACTIONS; Redox state; Thiol groups
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.11.186

Integrins belong to a family of transmembrane receptors that mediate cell migration and adhesion to ECM. Extracellular domains of integrin heterodimers contain cysteine-rich regions, which are potential sites of thiol-disulfide exchanges. Rearrangements of extracellular disulfide bonds regulate activation of integrin receptors by promoting transition from an inactive state into a ligand-binding competent state. Modifications of integrin disulfide bonds dependent on oxidation-reduction can be mediated by Protein Disulfide Isomerse (PDI). This paper provides evidences that binding to integrin ligands initiate changes in free thiol pattern on cell surface and that thiol-disulfide exchange mediated by PDI leads to activation of integrin subunit α11. By employing co-immunoprecipitation and confocal microscopy analysis we showed that α11β1 and PDI create complexes bounded by disulfide bonds. Using surface plasmon resonance we provide biochemical evidence that PDI can interact directly with integrin subunit α11. •Protein Disulfide Isomers can interact with α11 integrin in response to adhesion.•Complexes PDI- α11 are linked by disulfide bonds.•Free thiol blockers and PDI inhibitors blocks adhesion and migration mediated by α11 integrin.