A novel role for thioredoxin-related transmembrane protein TMX4 in platelet activation and thrombus formation.

Background: The functions of critical platelet proteins are controlled by thiol-disulfide exchanges, which are mediated by the protein disulfide isomerase (PDI) family. It has been shown that some PDI family members are important in platelet activation and thrombosis with distinct functions. TMX4, a membrane-type PDI family member, is expressed in platelets, but whether it has a role in platelet activation remains unknown.

Transmembrane thiol isomerase TMX1 counterbalances the effect of ERp46 to inhibit platelet activation and integrin αIIbβ3 function.

Background: Previous studies have shown that thiol isomerases such as ERp46 positively regulate platelet function by reducing integrin αIIbβ3 disulfides, and the transmembrane thiol isomerase TMX1 negatively regulates integrin αIIbβ3 activation. However, whether and how the positive and negative thiol isomerases interact with each other and their interactions participate in platelet activation remain unknown.

Objectives: To investigate whether and how TMX1 regulates the effect of ERp46 on platelet function.