Platelet protein disulphide isomerase (PDI) has a role in platelet aggregation, probably targeting a thiol-containing platelet surface protein. The thiol-containing P2Y12 ADP receptor is involved in aggregation induced by most agonists and may be the target of PDI. By excluding the P2Y 12 pathway and using the anti-PDI antibody RL90 this study showed that PDI targets a non-P2Y12 thiol-protein in aggregation. Anti-PDI inhibited signalling-independent activation of the thiol-containing fibrinogen receptor αIIbβ3 by Mn2+, suggesting that PDI directly interacts with αIIbβ3. The thiol-containing form of PDI increased on the platelet surface with platelet activation, suggesting that active PDI readily becomes available for redox regulation of αIIbβ3. Finally, using purified proteins PDI had greater ability to isomerize disulphide bonds than the αIIbβ3 integrin, which also has PDI-like activity. In summary, a mechanism exists in platelets to increase the functional form of surface PDI and this PDI has a non-P2Y12 target that may be αIIbβ3.
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