Normal prion protein trafficking in cultured human erythroblasts.
Normal prion protein (PrP(c)), an essential substrate for development of prion disease, is widely distributed in hematopoietic cells. Recent evidence that variant Creutzfeldt-Jakob disease can be transmitted by transfusion of red cell preparations has highlighted the need for a greater understanding of the biology of PrP(c) in blood and blood-forming tissues. Here, we show that in contrast to another glycosylphosphoinositol-anchored protein CD59, PrP(c) at the cell surface of cultured human erythroblasts is rapidly internalized through the endosomal pathway, where it colocalizes with the tetraspanin CD63. In the plasma membrane, PrP(c) colocalizes with the tetraspanin CD81. Cross-linking with anti-PrP(c) or anti-CD81 causes clustering of PrP(c) and CD81, suggesting they can share the same microdomain. These data are consistent with a role for tetraspanin-enriched microdomains in trafficking of PrP(c). These results, when taken together with recent evidence that exosomes released from cells as a result of endosomal-mediated recycling to the plasma membrane contain prion infectivity, provide a pathway for the propagation of prion diseases.
Griffiths
Rebecca E
RE
Bristol Institute for Transfusion Sciences, National Blood Service, Bristol, UK.
Heesom
Kate J
KJ
Anstee
David J
DJ
D015703:Antigens, CD / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D004900:Erythroblasts / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D021381:Protein Transport; D060225:Tetraspanin 28; D060149:Tetraspanin 30