title: Cellular prion protein released on exosomes from macrophages binds to Hsp70.
abstract: Prion diseases are infectious and fatal neurodegenerative disorders. The cellular prion protein (PrP(C)) converting into misfolded isoform of prion protein (PrP(Sc)) 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 PrP(Sc). So, understanding the PrP(C) trafficking in macrophages is important to explore the transport mechanism for PrP(Sc). Here, we isolated exosomes from the culture medium of Ana-1 macrophage cell line and investigated the PrP(C) trafficked by exosomes and the interaction of PrP(C) 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 PrP(C). And PrP(C) bound to Hsp70 both in intracellular environment and secreted exosomes. In contrast, PrP(C) had no interaction with marker proteins of exosomes, Tag101 and Flotillin-1. These results suggested that PrP(C) present in extracellular space might be externalized through secreted exosomes from macrophages, and Hsp70 may play roles in the process of PrP(C) released via secreted exosomes.
authors.affiliation: National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Wang
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D002478:Cells, Cultured; D005089:Exocytosis / Q000276:immunology / Q000502:physiology; D055354:Exosomes / Q000737:chemistry*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000139:chemically induced; D011328:Prions / Q000633:toxicity*; D017510:Protein Folding
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018621:PrPC Proteins; D011328:Prions