Mostrar el registro sencillo del ítem
dc.contributor.author | Villarroya-Beltri, Carolina | |
dc.contributor.author | Baixauli, Francesc | |
dc.contributor.author | Mittelbrunn, Maria | |
dc.contributor.author | Fernandez-Delgado, Irene | |
dc.contributor.author | Torralba, Daniel | |
dc.contributor.author | Moreno-Gonzalo, Olga | |
dc.contributor.author | Baldanta, Sara | |
dc.contributor.author | Enrich, Carlos | |
dc.contributor.author | Guerra, Susana | |
dc.contributor.author | Sanchez-Madrid, Francisco | |
dc.date.accessioned | 2017-10-20T10:33:51Z | |
dc.date.available | 2017-10-20T10:33:51Z | |
dc.date.issued | 2016 | |
dc.identifier | ISI:000388761600001 | |
dc.identifier.citation | Nat Commun. 2016; 7:13588 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5174 | |
dc.description.abstract | Exosomes are vesicles secreted to the extracellular environment through fusion with the plasma membrane of specific endosomes called multivesicular bodies (MVB) and mediate cell-to-cell communication in many biological processes. Posttranslational modifications are involved in the sorting of specific proteins into exosomes. Here we identify ISGylation as a ubiquitin-like modification that controls exosome release. ISGylation induction decreases MVB numbers and impairs exosome secretion. Using ISG15-knockout mice and mice expressing the enzymatically inactive form of the de-ISGylase USP18, we demonstrate in vitro and in vivo that ISG15 conjugation regulates exosome secretion. ISG15 conjugation triggers MVB co-localization with lysosomes and promotes the aggregation and degradation of MVB proteins. Accordingly, inhibition of lysosomal function or autophagy restores exosome secretion. Specifically, ISGylation of the MVB protein TSG101 induces its aggregation and degradation, being sufficient to impair exosome secretion. These results identify ISGylation as a novel ubiquitin-like modifier in the control of exosome production. | |
dc.description.sponsorship | We thank Dr K. Knobeloch, Dr A. Garcia-Sastre and Dr M.A. Alonso for providing reagents, and Dr S. Bartlett for assistance with English editing. C.E. is thankful to electron microscopy facility (campus Casanova), CCiT-University of Barcelona. This study was supported by grants SAF2014-55579-R from the Spanish Ministry of Economy and Competitiveness, INDISNET-S2011/BMD-2332 from the Comunidad de Madrid, Cardiovascular Network RD12-0042-0056 and PIE13/00041 from Instituto de Salud Carlos III (Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER), ERC-2011-AdG 294340-GENTRIS and COST-Action BM1202 to F.S.-M.; grant SAF2014-54623-R, FIS grant PI11/00127 (Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and Ministry of Health of Spain, State secretary of R+D and FEDER/FSE) and Bayer Group Grants4Grants (ID 2013-08-0982) to S.G.; and grant BFU2015-66785-P from the Spanish Ministry of Economy and Competitiveness to C.E.; Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). C.V.-B. was supported by FPU programme (Spanish Ministry of Education). M. M. is supported by MS14/00219 from Instituto de Salud Carlos III. | |
dc.language.iso | eng | |
dc.publisher | Nature Publishing Group | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | UBIQUITIN-LIKE PROTEIN | |
dc.subject | MULTIVESICULAR BODY FORMATION | |
dc.subject | INTERFERON-STIMULATED GENE | |
dc.subject | HUMAN-CELLS | |
dc.subject | AUTOPHAGIC VACUOLES | |
dc.subject | MEMBRANE-PROTEINS | |
dc.subject | ISG15 CONJUGATION | |
dc.subject | VIRAL RESISTANCE | |
dc.subject | PLASMA-MEMBRANE | |
dc.subject | LIGASE ACTIVITY | |
dc.title | ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 27882925 | |
dc.format.volume | 7 | |
dc.identifier.doi | 10.1038/ncomms13588 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Bayer Group | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1038/ncomms13588 | |
dc.identifier.journal | NATURE COMMUNICATIONS | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-54623-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BFU2015-66785-P | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-55579-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/294340/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12-0042-0056 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PIE13/00041 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI11/00127 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/MS14/00219 | es_ES |
dc.rights.accessRights | open access | es_ES |