Cellular prion protein released on exosomes from macrophages binds to Hsp70
Acta Biochimica et Biophysica Sinica,
2010, 42(5), 345-350. DOI: 10.1093/abbs/gmq028
Prion diseases are infectious and fatal neurodegenerative disorders. The cellular prion protein (PrPC) converting into misfolded isoform of prion protein (PrPSc) is responsible for prion disease infection. Immune system plays an important role in facilitating the spread of prion infections from the periphery to the central nervous system. Macrophages were considered associated with the transportation and replication of PrPSc. So, understanding the PrPC trafficking in macrophages is important to explore the transport mechanism for PrPSc. Here, we isolated exosomes from the culture medium of Ana-1 macrophage cell line and investigated the PrPC trafficked by exosomes and the interaction of PrPC with Hsp70 in secreted exosomes by western blotting, immunoelectron microscopy, and co-immunoprecipitation. The results showed that the isolated vesicles from the culture medium of macrophages were characterized by exosomes and bore PrPC. And PrPC bound to Hsp70 both in intracellular environment and secreted exosomes. In contrast, PrPC had no interaction with marker proteins of exosomes, Tag101 and Flotillin-1. These results suggested that PrPC present in extracellular space might be externalized through secreted exosomes from macrophages, and Hsp70 may play roles in the process of PrPC released via secreted exosomes.