Cellular prion protein is released on exosomes from activated platelets

Abstract

Cellular prion protein (PrP^C) is a glycophosphatidylinositol (GPI)–anchored protein, of unknown function, found in a number of tissues throughout the body, including several blood components of which platelets constitute the largest reservoir in humans. It is widely believed that a misfolded, protease-resistant form of PrP^C, PrP^Sc, is responsible for the transmissible spongiform encephalopathy (TSE) group of fatal neurodegenerative diseases. Although the pathogenesis of TSEs is poorly understood, it is known that PrP^C must be present in order for the disease to progress; thus, it is important to determine the physiologic function of PrP^C. Resolving the location of PrP^C in blood will provide valuable clues as to its function. PrP^C was previously shown to be on the alpha granule membrane of resting platelets. In the current study platelet activation led to the transient expression of PrP^C on the platelet surface and its subsequent release on both microvesicles and exosomes. The presence of PrP^C on platelet-derived exosomes suggests a possible mechanism for PrP^C transport in blood and for cell-to-cell transmission.