SUMOylation regulates protein cargo in small extracellular vesicles
Recent studies describe a new mechanism of intercellular communication mediated by secreted extracellular vesicles (EVs). Exosomes are small EVs (sEVs) released to the extracellular environment by the fusion of the endosomal pathway-related multivesicular bodies (containing intraluminal vesicles) wi...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | Chile |
| OAI Identifier: | oai:repositorio.anid.cl:10533/241929 |
| Acceso en línea: | https://hdl.handle.net/10533/241929 |
| Access Level: | acceso abierto |
| Palabra clave: | Ciencias Naturales Otras Ciencias Naturales |
| Sumario: | Recent studies describe a new mechanism of intercellular communication mediated by secreted extracellular vesicles (EVs). Exosomes are small EVs (sEVs) released to the extracellular environment by the fusion of the endosomal pathway-related multivesicular bodies (containing intraluminal vesicles) with the plasma membrane. Their diameter varies between 30 to 200 nm, although the presence of small vesicles in the same size range, but of other biological origin (such as the plasma membrane), cannot be discarded in biochemical sEV preparations. sEVs contain a molecular cargo consisting of lipids, proteins and nucleic acids. However, the loading mechanisms for these molecules have not been completely elucidated. In that line, the post translational modification SUMO (Small Ubiquitin-like Modifier) has been shown to impact the molecular cargo of sEVs. SUMO modification consists in covalent conjugation of lysine residues of target proteins with SUMO-1 or SUMO-2 proteins. This has been shown to constitute a sEV destination signal for selected proteins. In turn, astrocytes are an essential cell type of the central nervous system with homeostatic functions. The sEVs derived from astrocytes transfected with SUMO-2 contained an increased protein cargo per vesicle. By mass spectrometry, we detected proteins related with cell division, translation and transcription. In astrocytes treated with 2-D08 we observed an increase of the number of released sEVs and a decreased protein cargo in these sEVs. To change the physiological environment of astrocytes, they were treated with the stress hormone corticosterone, we found an increase of proteins conjugated with SUMO-2 and these sEVs contained an augmented protein cargo. Furthermore, to test whether astrocyte-derived sEVs obtained in these experimental conditions have a consequence on neuronal functions, we incubated neurons with sEVs from astrocytes treated with corticosterone or 2-D08. We found increased protein synthesis in neurons incubated with sEVs derived from astrocytes that had been exposed to corticosterone. No difference was found in protein synthesis in neurons incubated with sEVs from astrocytes treated with 2-D08 compared to neurons without sEVs, suggesting that the inhibition of SUMOylation prevents the loading of proteins relevant for protein synthesis in sEVs. |
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