2026-08-29T09:25:05Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51742024-09-27T08:49:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Villarroya-Beltri, Carolina
author
Baixauli, Francesc
author
Mittelbrunn, Maria
author
Fernandez-Delgado, Irene
author
Torralba, Daniel
author
Moreno-Gonzalo, Olga
author
Baldanta, Sara
author
Enrich, Carlos
author
Guerra, Susana
author
Sanchez-Madrid, Francisco
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea
funder
Bayer Group
funder
Fundación ProCNIC
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2017-10-20T10:33:51Z
2017-10-20T10:33:51Z
2016
Nat Commun. 2016; 7:13588
10.1038/ncomms13588
2041-1723
NATURE COMMUNICATIONS
27882925
http://hdl.handle.net/20.500.12105/5174
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.
eng
UBIQUITIN-LIKE PROTEIN
MULTIVESICULAR BODY FORMATION
INTERFERON-STIMULATED GENE
HUMAN-CELLS
AUTOPHAGIC VACUOLES
MEMBRANE-PROTEINS
ISG15 CONJUGATION
VIRAL RESISTANCE
PLASMA-MEMBRANE
LIGASE ACTIVITY
ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins
journal article
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https://repisalud.isciii.es/bitstreams/89176494-80d7-4d35-9812-27bc5af64040/download
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3913fbef2cc9d71244c9eeb311f2c80e
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ISGylationControlsExosomeSecretion_2016
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d2509f0badfb43f7b84a3316d3206939
67329
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ISGylationControlsExosomeSecretion_2016.txt