Introduction The thiolisomerases PDI and ERp57 are released to the platelet surface and contribute to several cellular responses. PDI is present in subcellular structures, not corresponding to α - and δ -granules, and lysosomes. It was, however, shown to co-localise with TLR9 in T-granules. The subcellular localisation of other platelet thiolisomerases or their mechanisms of translocation to the cell surface have not been established.
Hypothesis and Methods Using spinning disk confocal microscopy we explored whether ERp57 and PDI co-localise in resting and activated platelets and whether actin polymerization regulates their translocation to the platelet surface.
Results In resting platelets, PDI and ERp57 were organized in granular structures both on the platelet surface and in the cytoplasm where they co-localised (Pearson's correlation coefficient=0.597±0.08, mean±SD). They neither co-distributed with P-selectin, an α -granule membrane marker, nor with TLR9, a marker of T-granules. Upon platelet activation, the thiolisomerases still co-distributed and migrated to the surface (Pearson's correlation coefficient=0.533±0.08, mean±SD). Inhibiting actin polymerization with latrunculin A, decreased P-selectin exposure on the platelet surface and prevented agonist-induced platelet shape change, as shown by tubulin staining. Importantly, latrunculin A also blocked the translocation of PDI and ERp57 from internal granular structures to the platelet surface.
Conclusions In resting platelets PDI and ERp57 are organized, and partially co-localised, in punctuate structures different from α- or T-granules. Actin polymerization during platelet activation exerts a fundamental role in the relocalisation of PDI and ERp57 to the platelet surface, thus suggesting that thiolisomerases undergo a bonfide secretory mechanism.
- CARDIAC PROCEDURES AND THERAPY
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