Fevrier Benoit, Vilette Didier, Archer Fabienne, Loew Damarys, Faigle Wolfgang, Vidal Michel, Laude Hubert, Raposo Graça
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Institut Curie, 75005 Paris, France.
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9683-8. doi: 10.1073/pnas.0308413101. Epub 2004 Jun 21.
Prion diseases are infectious neurodegenerative disorders linked to the accumulation in the central nervous system of the abnormally folded prion protein (PrP) scrapie (PrPsc), which is thought to be the infectious agent. Once present, PrPsc catalyzes the conversion of naturally occurring cellular PrP (PrPc) to PrPsc. Prion infection is usually initiated in peripheral organs, but the mechanisms involved in infectious spread to the brain are unclear. We found that both PrPc and PrPsc were actively released into the extracellular environment by PrP-expressing cells before and after infection with sheep prions, respectively. Based on Western blot with specific markers, MS, and morphological analysis, our data revealed that PrPc and PrPsc in the medium are associated with exosomes, membranous vesicles that are secreted upon fusion of multivesicular endosomes with the plasma membrane. Furthermore, we found that exosomes bearing PrPsc are infectious. Our data suggest that exosomes may contribute to intercellular membrane exchange and the spread of prions throughout the organism.
朊病毒疾病是一类传染性神经退行性疾病，与异常折叠的朊病毒蛋白（PrP）瘙痒病（PrPsc）在中枢神经系统中的积累有关，PrPsc被认为是感染因子。一旦出现，PrPsc会催化天然存在的细胞PrP（PrPc）转化为PrPsc。朊病毒感染通常在外周器官开始，但感染扩散至大脑的机制尚不清楚。我们发现，在感染绵羊朊病毒之前和之后，表达PrP的细胞分别将PrPc和PrPsc主动释放到细胞外环境中。基于使用特异性标记物的蛋白质印迹、质谱分析和形态学分析，我们的数据表明，培养基中的PrPc和PrPsc与外泌体相关，外泌体是多囊泡内体与质膜融合后分泌的膜性囊泡。此外，我们发现携带PrPsc的外泌体具有传染性。我们的数据表明，外泌体可能有助于细胞间膜交换以及朊病毒在整个生物体中的传播。
