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...

Descripción completa

Detalles Bibliográficos
Autor: Fernandez, Anllely
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
id CL_3ac4ce91a6f1ab0f4a3cff84483bbbc6
oai_identifier_str oai:repositorio.anid.cl:10533/241929
network_acronym_str CL
network_name_str Chile
repository_id_str
dc.title.es_CL.fl_str_mv SUMOylation regulates protein cargo in small extracellular vesicles
title SUMOylation regulates protein cargo in small extracellular vesicles
spellingShingle SUMOylation regulates protein cargo in small extracellular vesicles
Fernandez, Anllely
Ciencias Naturales
Otras Ciencias Naturales
title_short SUMOylation regulates protein cargo in small extracellular vesicles
title_full SUMOylation regulates protein cargo in small extracellular vesicles
title_fullStr SUMOylation regulates protein cargo in small extracellular vesicles
title_full_unstemmed SUMOylation regulates protein cargo in small extracellular vesicles
title_sort SUMOylation regulates protein cargo in small extracellular vesicles
dc.creator.none.fl_str_mv Fernandez, Anllely
author Fernandez, Anllely
author_facet Fernandez, Anllely
author_role author
dc.contributor.advisor.none.fl_str_mv Wyneken, Ursula
dc.contributor.institution.es_CL.fl_str_mv UNIVERSIDAD DE LOS ANDES
dc.subject.oecd1n.es_CL.fl_str_mv Ciencias Naturales
topic Ciencias Naturales
Otras Ciencias Naturales
dc.subject.oecd2n.es_CL.fl_str_mv Otras Ciencias Naturales
description 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.
publishDate 2020
dc.date.accessioned.none.fl_str_mv 2020-04-27T13:42:13Z
2022-08-19T21:29:52Z
dc.date.available.none.fl_str_mv 2020-04-27T13:42:13Z
2022-08-19T21:29:52Z
dc.date.issued.es_CL.fl_str_mv 2020
dc.date.embargo.es_CL.fl_str_mv info:eu-repo/date/embargoEnd/2021-12-31
dc.type.none.fl_str_mv Tesis Doctorado
dc.type.driver.es_CL.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.tesis.none.fl_str_mv Tesis
format doctoralThesis
status_str publishedVersion
dc.identifier.folio.es_CL.fl_str_mv 21150958
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/241929
identifier_str_mv 21150958
url https://hdl.handle.net/10533/241929
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.projectid.es_CL.fl_str_mv info:eu-repo/grantAgreement//21150958
dc.relation.set.none.fl_str_mv info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488
dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivs 3.0 Chile
dc.rights.driver.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
rights_invalid_str_mv Attribution-NonCommercial-NoDerivs 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
eu_rights_str_mv openAccess
bitstream.url.fl_str_mv https://repositorio.anid.cl/bitstreams/b638d49b-525e-4cf7-8436-99efa37c72d6/download
https://repositorio.anid.cl/bitstreams/7fd576d4-b5a3-4db6-86f0-0395fb7c174c/download
https://repositorio.anid.cl/bitstreams/de43ed02-67cf-48f7-b433-acb54ed6a7f8/download
https://repositorio.anid.cl/bitstreams/348967c2-ab27-4c08-881a-4288340b4242/download
https://repositorio.anid.cl/bitstreams/63944753-755a-47c0-b5f9-78f186794f47/download
bitstream.checksum.fl_str_mv db3e1f007ec6e8cfdc0ce8098de89c55
f97bcfdf58f3e17b5cec231112dab5b1
593a6e7305c66c56041a9f9e15a649c1
1acaa09a6348caf9af083b592d362e16
82f8c4f99ce22b9781a5fe219e640c3e
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
_version_ 1843518825558966272
spelling UNIVERSIDAD DE LOS ANDESFernandez, Anllely2020https://hdl.handle.net/10533/241929http://purl.org/coar/access_right/c_abf2Otras Ciencias NaturalesCiencias NaturalesSUMOylation regulates protein cargo in small extracellular vesiclesWyneken, UrsulaUNIVERSIDAD DE LOS ANDESChileFernandez, Anllely2020-04-27T13:42:13Z2022-08-19T21:29:52Z2020-04-27T13:42:13Z2022-08-19T21:29:52Zinfo:eu-repo/date/embargoEnd/2021-12-312020Recent 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.Pendiente de publicación21150958https://hdl.handle.net/10533/241929instname: Conicytreponame: Repositorio Digital RI2.0info:eu-repo/grantAgreement//21150958info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488Attribution-NonCommercial-NoDerivs 3.0 Chileinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/Ciencias NaturalesOtras Ciencias NaturalesSUMOylation regulates protein cargo in small extracellular vesiclesTesis Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionTesisTesishttps://hdl.handle.net/10533/24192960ab7d83-7311-4dcb-8490-b79d22da1a7dvirtual::59024-160ab7d83-7311-4dcb-8490-b79d22da1a7dvirtual::59024-1ORIGINALTesis AFR v.final.pdfapplication/pdf10337074https://repositorio.anid.cl/bitstreams/b638d49b-525e-4cf7-8436-99efa37c72d6/downloaddb3e1f007ec6e8cfdc0ce8098de89c55MD51CC-LICENSElicense_rdfapplication/octet-stream1232https://repositorio.anid.cl/bitstreams/7fd576d4-b5a3-4db6-86f0-0395fb7c174c/downloadf97bcfdf58f3e17b5cec231112dab5b1MD52LICENSElicense.txttext/plain1779https://repositorio.anid.cl/bitstreams/de43ed02-67cf-48f7-b433-acb54ed6a7f8/download593a6e7305c66c56041a9f9e15a649c1MD53TEXTTesis AFR v.final.pdf.txtExtracted texttext/plain168447https://repositorio.anid.cl/bitstreams/348967c2-ab27-4c08-881a-4288340b4242/download1acaa09a6348caf9af083b592d362e16MD54THUMBNAILTesis AFR v.final.pdf.jpgIM Thumbnailimage/jpeg4713https://repositorio.anid.cl/bitstreams/63944753-755a-47c0-b5f9-78f186794f47/download82f8c4f99ce22b9781a5fe219e640c3eMD5510533/241929oai:repositorio.anid.cl:10533/2419292023-07-24 05:32:28.213http://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/embargoedAccesshttps://repositorio.anid.clRepositorio ANIDaletelier@anid.clTGljZW5jaWEgZGUgRGlzdHJpYnVjacOzbiBObyBFeGNsdXNpdmEKCkFsIGZpcm1hciB5IHByZXNlbnRhciBlc3RhIGxpY2VuY2lhICwgdXN0ZWQgKGVsIGF1dG9yKGVzKSBvIHRpdHVsYXIgZGUgZGVyZWNob3MgZGUgYXV0b3IpIGdhcmFudGl6YSBhIGxhIENvbWlzacOzbiBOYWNpb25hbCBkZSBJbnZlc3RpZ2FjacOzbiBDaWVudMOtdGljYSB5IFRlY25vbMOzZ2ljYSAoQ09OSUNZVCkgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNpciAsIHRyYWR1Y2lyIChjb21vIHNlIGRlZmluZSBtw6FzIGFiYWpvKSAsIHkvbyBkaXN0cmlidWlyIHN1IGRvY3VtZW50byAoaW5jbHV5ZW5kbyBlbCByZXN1bWVuKSBlbiB0b2RvIGVsIG11bmRvIGVuIGZvcm1hIGltcHJlc2EgeSBlbiBmb3JtYXRvIGVsZWN0csOzbmljbyB5IGVuIGN1YWxxdWllciBtZWRpbywgaW5jbHV5ZW5kbywgcGVybyBubyBsaW1pdGFkbyBhLCBhdWRpbyBvIHbDrWRlby4KClVzdGVkIGFjZXB0YSBxdWUgQ09OSUNZVCBwdWVkZSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXJsbyBhIGN1YWxxdWllciBtZWRpbyBvIGZvcm1hdG8gcGFyYSBlbCBmaW4gZGUgbGEgY29uc2VydmFjacOzbi4KClRhbWJpw6luIGFjZXB0YSBxdWUgQ09OSUNZVCBwdWVkZSB0ZW5lciBtw6FzIGRlIHVuYSBjb3BpYSBkZSBlc3RlIGRvY3VtZW50byBwYXJhIGZpbmVzIGRlIHNlZ3VyaWRhZCwgY29waWFzIGRlIHNlZ3VyaWRhZCB5IGNvbnNlcnZhY2nDs24uCgpVc3RlZCBkZWNsYXJhIHF1ZSBlbCBkb2N1bWVudG8gZXMgdW4gdHJhYmFqbyBvcmlnaW5hbCwgeSBxdWUgdXN0ZWQgdGllbmUgZWwgZGVyZWNobyBkZSBvdG9yZ2FyIGxvcyBkZXJlY2hvcyBjb250ZW5pZG9zIGVuIGVzdGEgbGljZW5jaWEuIFRhbWJpw6luIGRlY2xhcmEgcXVlIHN1IHBldGljacOzbiBubywgYSBsbyBtZWpvciBkZSBzdSBjb25vY2ltaWVudG8sIGluZnJpbmdlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZSBuYWRpZS4KClNpIGVsIGRvY3VtZW50byBjb250aWVuZSBtYXRlcmlhbGVzIGRlIGxvcyBxdWUgbm8gdGllbmVuIGRlcmVjaG9zIGRlIGF1dG9yICwgdXN0ZWQgZGVjbGFyYSBxdWUgaGEgb2J0ZW5pZG8gZWwgcGVybWlzbyBzaW4gcmVzdHJpY2Npw7NuIGRlbCBwcm9waWV0YXJpbyBkZSBsb3MgZGVyZWNob3MgcmVxdWVyaWRvcyBwb3IgZXN0YSBsaWNlbmNpYSB5IHF1ZSBlc2UgbWF0ZXJpYWwgY3V5b3MgZGVyZWNob3Mgc29uIGRlIHRlcmNlcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIHkgcmVjb25vY2lkbyBlbiBlbCB0ZXh0byBvIGNvbnRlbmlkbyBkZWwgZG9jdW1lbnRvIGVudHJlZ2Fkby4KClNJIEVMIEVOVsONTyBTRSBCQVNBIEVOIEVMIFRSQUJBSk8gUVVFIEhBIFNJRE8gUEFUUk9OQURPIE8gQVBPWUFETyBQT1IgQUxHVU5BIElOU1RJVFVDScOTTiBRVUUgTk8gU0VBIENPTklDWVQsIFVTVEVEIEFDRVBUQSBRVUUgSEEgQ1VNUExJRE8gQSBDVUFMUVVJRVIgREVSRUNITyBERSBSRVZJU0nDk04gVSBPVFJBUyBPQkxJR0FDSU9ORVMgUkVRVUVSSURBUyBQT1IgRElDSE8gQ09OVFJBVE8gTyBBQ1VFUkRPLgoKQ09OSUNZVCBpZGVudGlmaWNhcsOhIGNsYXJhbWVudGUgc3Ugbm9tYnJlKGVzKSBjb21vIGVsIGF1dG9yKGVzKSBvIHByb3BpZXRhcmlvKHMpIGRlIGxhIHByZXNlbnRhY2nDs24gLCB5IG5vIGhhcsOhIG5pbmd1bmEgYWx0ZXJhY2nDs24sIGV4Y2VwdG8gc2Vnw7puIGxvIHBlcm1pdGlkbyBwb3IgbGEgbGljZW5jaWEsIHBhcmEgc3UgcHJlc2VudGFjacOzbi4K
score 15,811543

Similares en LA Referencia