Exosome target cell selection and the importance of exosomal tetraspanins: a hypothesis
Exosome target cell selection and the importance of exosomal tetraspanins: a hypothesis
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DOI：
10.1042/bst0390559
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发表时间：
2011-04-01
影响因子：
3.9
通讯作者：
Zoeller, Margot
中科院分区：
文献类型：
--
作者：
Rana, Sanyukta;Zoeller, Margot
外泌体来源于MVBs （rnultivesular body）的限制膜。它们携带并将选定的膜和细胞质蛋白、mRNA和microRNA转移到靶细胞中。正是由于这种信息的运输，外泌体被认为是多种疾病最有前途的治疗工具。然而，尽管对外泌体组成的了解正在迅速增加，但对外泌体的选择性招募模式以及靶细胞选择知之甚少。我们认为这项任务至少有一部分是由四联蛋白承担的。四联蛋白参与形态发生、裂变和融合过程，在外泌体中富集，我们之前的工作表明，不同的四联蛋白外泌体的招募遵循非常有选择性的途径，包括四联蛋白网的重排。此外，只有表达一组特定的四跨蛋白和相关分子的外泌体才能靶向内皮细胞，从而促进血管生成和血管生成。基于这些发现，我们假设(i)外泌体的蛋白质组装和microRNA的可能募集将在很大程度上由tetraspanins调节，（ii） tetraspanins解释了靶细胞选择和靶细胞对外泌体的紧密相互作用/摄取。外泌体预示着一个意想不到的强大的细胞间通讯途径。外泌体如何收集和传递信息的答案将允许使用自然的概念来处理故障。
Exosomes are derived from limiting membranes of MVBs (rnultivesicular bodies). They carry and transfer selected membrane and cytoplasmic proteins, mRNA and microRNA into target cells. It is due to this shipping of information that exosomes are considered to be the most promising therapeutic tool for multiple diseases. However, whereas knowledge on the composition of exosomes is rapidly increasing, the mode of selective recruitment into exosomes as well as target cell selection is poorly understood. We suggest that at least part of this task is taken over by tetraspanins. Tetraspanins, which are involved in morphogenesis, fission and fusion processes, are enriched in exosomes, and our previous work revealed that the recruitment of distinct tetraspanins into exosomes follows very selective routes, including a rearrangement of the tetraspanin web. Furthermore, only exosomes expressing a defined set of tetraspanins and associated molecules target endothelial cells, thereby contributing to angiogenesis and vasculogenesis. On the basis of these findings we hypothesize (i) that the protein assembly of exosomes and possibly the recruitment of microRNA will be regulated to a large extent by tetraspanins and (ii) that tetraspanins account for target cell selection and the tight interaction/uptake of exosomes by the target cell. Exosomes herald an unanticipated powerful path of cell-cell communication. An answer to how exosomes collect and transfer information will allow the use of Nature's concept to cope with malfunctions.