Hsp70 binds to PrPC in the process of PrPC release via exosomes from THP-1 monocytes.
PrPC (cellular prion protein) is a GPI (glycophosphatidylinositol)-anchored protein present on the surface of a number of peripheral blood cells. PrPC must be present for the generation and propagation of pathogenic conformer [PrPSc (scrapie prion protein)], which is a conformational conversion form of PrPC and has a central role in transmissible spongiform encephalopathies. It is important to determine the transportation mechanism of normal PrPC between cells. Exosomes are membrane vesicles released into the extracellular space upon fusion of multivesicular endosomes with the plasma membrane. We have identified that THP-1 monocytes can secrete exosomes to culture medium, and the secreted exosomes can bear PrPC. We also found that Hsp70 interacts with PrPC not only in intracellular environment, but in the secreted exosomes. However, the specific markers of exosomes, Tsg101 and flotillin-1, were found with no interaction with PrPC. Our results demonstrated that PrPC can be released from THP-1 monocytes via secreted exosomes, and in this process, Hsp70 binds to PrPC, which suggests that Hsp70 may play a potential functional role in the release of PrPC.
State Key Laboratories for Agrobiotechnology, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, Peoples Republic of China.
Gui-Hua
GH
Wang
Xiang-Mei
XM
Zhou
Yu
Y
Bai
Xiao-Min
XM
Yin
Li-Feng
LF
Yang
Deming
D
Zhao
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D018621:PrPC Proteins; D014157:Transcription Factors; D000099177:Tsg101 Protein; C106354:flotillins