Prions and exosomes:: From PrPc trafficking to PrPsc propagation
Prions and exosomes:: From PrPc trafficking to PrPsc propagation
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DOI：
10.1016/j.bcmd.2005.06.013
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发表时间：
2005-09-01
影响因子：
2.3
通讯作者：
Raposo, G
中科院分区：
文献类型：
--
作者：
Porto-Carreiro, I;Février, B;Raposo, G
外泌体是多泡内体与细胞表面融合后释放到细胞外环境中的膜囊泡。外泌体分泌可以被细胞用于喷射靶向多泡体的管腔内囊泡的分子，但是特定的细胞类型可以利用外泌体作为细胞间通讯装置，用于在细胞之间转移蛋白质和脂质。糖基磷脂酰肌醇连接的朊病毒蛋白（PrP）在其正常（PrPc）和scrappie（PrPsc）构象与外来体。靶向含有正常细胞PrP的外泌体可以赋予不表达PrP的细胞对朊病毒增殖的易感性。此外，携带蛋白酶-K抗性PrPsc的外泌体是感染性的，这表明由感染细胞分泌的外泌体可以作为朊病毒繁殖的载体的模型。因此，细胞可以利用内体衍生的外泌体的性质在正常和病理情况下彼此通信，从而提供细胞间通信的新途径，并因此提供病原体传播的新途径。这些发现开启了一种可能性，即可以从对涉及外泌体形成、分泌和靶向的机制的见解中设想干扰这种非常规病原体的运输的方法。(c)2005年爱思唯尔公司All rights reserved.
Exosomes are membrane vesicles released into the extracellular environment upon exocytic fusion of multivesicular endosomes with the cell surface. Exosome secretion can be used by cells to eject molecules targeted to intraluminal vesicles of multivesicular bodies, but particular cell types may exploit exosomes as intercellular communication devices for transfer of proteins and lipids among cells. The glycosylphosphatyidylinositol-linked prion protein (PrP) in both its normal (PrPc) and scrappie (PrPsc) conformation is associated with exosomes. Targeting of exosomes containing the normal cellular PrP could confer susceptibility of cells that do not express PrP to prion multiplication. Furthermore, exosomes bearing proteinase-K resistant PrPsc are infectious, suggesting a model in which exosomes secreted by infected cells could serve as vehicles for propagation of prions. Thus, cells may exploit the nature of endosome-derived exosomes to communicate with each other in normal and pathological situations, providing for a novel route of cell-to-cell communication and therefore of pathogen transmission. These findings open the possibility that methods to interfere with trafficking of such unconventional pathogens could be envisioned from insights on the mechanisms involved in exosome formation, secretion and targeting. (c) 2005 Elsevier Inc. All rights reserved.