Vascular Pathophysiology Research Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Servicio de Inmunología, Instituto Investigación Sanitaria Princesa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Cell Mol Life Sci. 2018 Jan;75(1):1-19. doi: 10.1007/s00018-017-2690-y. Epub 2017 Oct 27.
Extracellular vesicles (EVs) are released by cells to the extracellular environment to mediate inter-cellular communication. Proteins, lipids, nucleic acids and metabolites shuttled in these vesicles modulate specific functions in recipient cells. The enrichment of selected sets of proteins in EVs compared with global cellular levels suggests the existence of specific sorting mechanisms to specify EV loading. Diverse post-translational modifications (PTMs) of proteins participate in the loading of specific elements into EVs. In this review, we offer a perspective on PTMs found in EVs and discuss the specific role of some PTMs, specifically Ubiquitin and Ubiquitin-like modifiers, in exosomal sorting of protein components. The understanding of these mechanisms will provide new strategies for biomedical applications. Examples include the presence of defined PTM marks on EVs as novel biomarkers for the diagnosis and prognosis of certain diseases, or the specific import of immunogenic components into EVs for vaccine generation.
细胞外囊泡 (EVs) 被释放到细胞外环境中，以介导细胞间通讯。这些囊泡中转运的蛋白质、脂质、核酸和代谢物调节受体细胞的特定功能。与全局细胞水平相比，EVs 中特定蛋白质组的富集表明存在特定的分选机制来指定 EV 的装载。蛋白质的多种翻译后修饰 (PTMs) 参与了特定元件装入 EVs 的过程。在这篇综述中，我们提供了对 EVs 中发现的 PTMs 的观点，并讨论了一些 PTMs 的特定作用，特别是泛素和泛素样修饰物，在蛋白质成分的外泌体分选中的作用。对这些机制的理解将为生物医学应用提供新的策略。例如，EVs 上存在特定的 PTM 标记，可作为某些疾病诊断和预后的新型生物标志物，或者将免疫原性成分特异性导入 EVs 用于疫苗生成。
