Protein disulfide isomerase mediates integrin-dependent adhesion.
Cell adhesion is mediated by the integrin adhesion receptors. Receptor-ligand interaction involves conformational changes in the receptor, but the underlying mechanism remains unclear. Our earlier work implied a role for sulfhydryls in integrin response to ligand binding in the intact blood platelet. We now show that non-penetrating blockers of free sulfhydryls inhibit beta(1) and beta(3) integrin-mediated platelet adhesion regardless of the affinity state of the integrin. Removal of the inhibitors prior to adhesion fully restores adhesion despite the irreversible nature of inhibitor-thiol interaction, indicating sulfhydryl exposure in response to adhesion. We further show that blocking protein disulfide isomerase (PDI) inhibits adhesion. These data indicate that: (a) ecto-sulfhydryls are necessary for integrin-mediated platelet adhesion; (b) disulfide exchange takes place during this process; (c) surface PDI is involved in integrin-mediated adhesion.
Lahav
J
J
Coagulation Laboratory, Institute of Haematology, Rubin Medical Center, Petah Tiqva, Israel. jlahav@netvision.net.il
Gofer-Dadosh
N
N
Luboshitz
J
J
Hess
O
O
Shaklai
M
M
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology*; D002448:Cell Adhesion; D003094:Collagen / Q000378:metabolism; D004220:Disulfides; D005033:Ethylmaleimide / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D004220:Disulfides; D005353:Fibronectins; D016023:Integrins; D008565:Membrane Proteins; D000644:Quaternary Ammonium Compounds; D013439:Sulfhydryl Reagents; D002731:4-Chloromercuribenzenesulfonate; C027344:bromotrimethylammoniobimane; D005340:Fibrinogen; D003094:Collagen; D019704:Protein Disulfide-Isomerases; D008274:Magnesium; D005033:Ethylmaleimide