Tetherin is an exosomal tether
Tetherin is an exosomal tether
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DOI：
10.7554/elife.17180
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发表时间：
2016-09-22
期刊：
影响因子：
7.7
通讯作者：
Robinson, Margaret S.
中科院分区：
文献类型：
--
作者：
Edgar, James R.;Manna, Paul T.;Robinson, Margaret S.
外泌体是当内体与质膜融合时释放的细胞外囊泡。它们与健康和疾病中的各种功能有关，包括细胞间通讯、抗原呈递、朊病毒传播和肿瘤细胞转移。在这里，我们表明，在HeLa细胞中的液泡ATP酶的失活导致外泌体，显示内吞示踪剂，胆固醇和CD63的生产显着增加。外泌体仍然聚集在细胞表面上，类似于逆转录病毒，其通过栓蛋白附着在质膜上。为了确定拴系蛋白是否也附着外泌体，我们将其敲除，发现质膜相关外泌体减少4倍，同时排出到培养基中的外泌体增加。这种表型可以被野生型系链蛋白拯救，但不能被缺乏GPI锚的系链蛋白拯救。我们认为，tetherin可能在外来体的命运中发挥关键作用，决定它们是否参与长距离或短距离的相互作用。
Exosomes are extracellular vesicles that are released when endosomes fuse with the plasma membrane. They have been implicated in various functions in both health and disease, including intercellular communication, antigen presentation, prion transmission, and tumour cell metastasis. Here we show that inactivating the vacuolar ATPase in HeLa cells causes a dramatic increase in the production of exosomes, which display endocytosed tracers, cholesterol, and CD63. The exosomes remain clustered on the cell surface, similar to retroviruses, which are attached to the plasma membrane by tetherin. To determine whether tetherin also attaches exosomes, we knocked it out and found a 4-fold reduction in plasma membrane-associated exosomes, with a concomitant increase in exosomes discharged into the medium. This phenotype could be rescued by wild-type tetherin but not tetherin lacking its GPI anchor. We propose that tetherin may play a key role in exosome fate, determining whether they participate in long-range or short-range interactions.