Cellular prion protein released on exosomes from macrophages binds to Hsp70

• Published in: Acta biochimica et biophysica Sinica 2010-05, Vol.42 (5), p.345-350
• Main Authors: Wang, Guihua, Zhou, Xiangmei, Bai, Yu, Zhang, Zhongqiu, Zhao, Deming
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Exocytosis - immunology; Exocytosis - physiology; Exosomes - chemistry; HSP70 Heat-Shock Proteins - metabolism; Humans; Macrophages - metabolism; Macrophages - pathology; Prion Diseases - chemically induced; Prions - toxicity; Protein Folding; PrPC Proteins - metabolism; 中枢神经系统; 巨噬细胞; 朊病毒疾病; 朊蛋白; 热休克蛋白70; 细胞分泌; 细胞培养液
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmq028

Prion diseases are infectious and fatal neurodegenerative disorders. The cellular prion protein （PrP^C） converting into misfolded isoform of prion protein （PrP^C） 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 PrPso. So, understanding the PrP^C 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 PrP^C. 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 PrP^C released via secreted exosomes.