Porto-Carreiro Isabel, Février Benoît, Paquet Sophie, Vilette Didier, Raposo Graça
Institut Curie, CNRS UMR 144, 75248 Paris, France.
Blood Cells Mol Dis. 2005 Sep-Oct;35(2):143-8. doi: 10.1016/j.bcmd.2005.06.013.
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.
外泌体是多囊泡内体与细胞表面发生胞吐融合后释放到细胞外环境中的膜泡。细胞可利用外泌体分泌来排出靶向多囊泡体内腔泡的分子，但特定细胞类型可能会将外泌体用作细胞间通讯装置，用于细胞间蛋白质和脂质的传递。正常构象（PrPc）和瘙痒病构象（PrPsc）的糖基磷脂酰肌醇连接的朊病毒蛋白（PrP）均与外泌体相关。含有正常细胞PrP的外泌体靶向作用可能会使不表达PrP的细胞对朊病毒增殖敏感。此外，携带蛋白酶K抗性PrPsc的外泌体具有传染性，这提示了一种模型，即受感染细胞分泌的外泌体可作为朊病毒传播的载体。因此，细胞可能利用内体来源外泌体的特性在正常和病理情况下相互通讯，提供了一种细胞间通讯的新途径，从而也是病原体传播的新途径。这些发现开启了一种可能性，即可以从对外泌体形成、分泌和靶向机制的深入了解中设想出干扰此类非常规病原体运输的方法。
