Cells release prions in association with exosomes
Cells release prions in association with exosomes
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DOI：
10.1073/pnas.0308413101
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发表时间：
2004-06-29
影响因子：
11.1
通讯作者：
Raposo, G
中科院分区：
文献类型：
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作者：
Fevrier, B;Vilette, D;Raposo, G
朊病毒疾病是与异常折叠的朊病毒蛋白（PrP）瘙痒症（PrPsc）在中枢神经系统中的积累相关的感染性神经退行性疾病，其被认为是感染因子。一旦存在，PrPsc催化天然存在的细胞PrP（PrPc）转化为PrPsc。朊病毒感染通常起始于外周器官，但感染性扩散至大脑的机制尚不清楚。我们发现，这两个PrPc和PrPsc主动释放到细胞外环境的PrP表达细胞感染绵羊朊病毒之前和之后，分别。基于具有特异性标记的蛋白质印迹、MS和形态学分析，我们的数据显示培养基中的PrPc和PrPsc与外泌体、多泡内体与质膜融合后分泌的膜囊泡相关。此外，我们发现携带PrPsc的外泌体具有感染性。我们的数据表明，外泌体可能有助于细胞间膜交换和朊病毒在整个生物体中的传播。
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.