State Key Laboratories for Agrobiotechnology, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, Peoples Republic of China.
Cell Biol Int. 2011 Jun;35(6):553-8. doi: 10.1042/CBI20090391.
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.
PrPC（细胞朊蛋白）是一种 GPI（糖磷脂酰肌醇）锚定蛋白，存在于许多外周血细胞的表面。PrPC 必须存在才能产生和传播致病性构象体 [PrPSc（瘙痒朊病毒蛋白）]，这是 PrPC 的构象转换形式，在传染性海绵状脑病中起核心作用。确定正常 PrPC 在细胞间的运输机制非常重要。外泌体是多泡内体与质膜融合时释放到细胞外空间的膜囊泡。我们已经确定 THP-1 单核细胞可以向培养基中分泌外泌体，并且分泌的外泌体可以携带 PrPC。我们还发现 Hsp70 不仅在细胞内环境中与 PrPC 相互作用，而且在分泌的外泌体中也与 PrPC 相互作用。然而，外泌体的特定标志物 Tsg101 和 flotillin-1 与 PrPC 没有相互作用。我们的结果表明，PrPC 可以通过分泌的外泌体从 THP-1 单核细胞中释放出来，在此过程中，Hsp70 与 PrPC 结合，这表明 Hsp70 可能在外泌体释放 PrPC 中发挥潜在的功能作用。
