Normal prion protein trafficking in cultured human erythroblasts
Normal prion protein trafficking in cultured human erythroblasts
复制标题
DOI：
10.1182/blood-2007-04-085183
复制
发表时间：
2007-12-15
期刊：
影响因子：
20.3
通讯作者：
Anstee, David J.
中科院分区：
文献类型：
--
作者：
Griffiths, Rebecca E.;Heesom, Kate J.;Anstee, David J.
普恩蛋白(PrPc)广泛分布于造血细胞中，是普恩疾病发生发展的重要底物。最近有证据表明，变异型克雅氏病可以通过输注红细胞制剂传播，这突出表明需要更多地了解血液和造血组织中PrPc的生物学。在这里，我们发现与另一种糖基磷酸肌醇锚定蛋白CD59不同的是，培养的人红细胞表面的PrPc通过内体途径迅速内化，在那里它与Tetraspanin CD63共存。在质膜上，PrPc与Tetraspanin CD81共定位。与抗PrPc或抗CD81的交联会导致PrPc和CD81的聚集，表明它们可以共享相同的微域。这些数据与PrPC贩运的主要情况是一致的。这些结果与最近的证据表明，由于内体介导的再循环到质膜而从细胞释放的外切体含有普恩感染性，为普恩疾病的传播提供了一条途径。
Normal prion protein (PrPc), 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 PrPc in blood and blood-forming tissues. Here, we show that in contrast to another glycosylphosphoinositol-anchored protein CD59, PrPc 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, PrPc colocalizes with the tetraspanin CD81. Cross-linking with anti-PrPc or anti-CD81 causes clustering of PrPc and CD81, suggesting they can share the same microdomain. These data are consistent with mains in trafficking of PrPc. 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.