Titre
Intracellular trafficking of interleukin-1 receptor I requires Tollip.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Brissoni, B.
Auteure/Auteur
Agostini, L.
Auteure/Auteur
Kropf, M.
Auteure/Auteur
Martinon, F.
Auteure/Auteur
Swoboda, V.
Auteure/Auteur
Lippens, S.
Auteure/Auteur
Everett, H.
Auteure/Auteur
Aebi, N.
Auteure/Auteur
Janssens, S.
Auteure/Auteur
Meylan, E.
Auteure/Auteur
Felberbaum-Corti, M.
Auteure/Auteur
Hirling, H.
Auteure/Auteur
Gruenberg, J.
Auteure/Auteur
Tschopp, J.
Auteure/Auteur
Burns, K.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0960-9822
Statut éditorial
Publié
Date de publication
2006-11-21
Volume
16
Numéro
22
Première page
2265
Dernière page/numéro d’article
2270
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Interleukin-1 receptor (IL-1RI) is a master regulator of inflammation and innate immunity. When triggered by IL-1beta, IL-1RI aggregates with IL-1R-associated protein (IL-1RAcP) and forms a membrane proximal signalosome that potently activates downstream signaling cascades. IL-1beta also rapidly triggers endocytosis of IL-1RI. Although internalization of IL-1RI significantly impacts signaling, very little is known about trafficking of IL-1RI and therefore about precisely how endocytosis modulates the overall cellular response to IL-1beta. Upon internalization, activated receptors are often sorted through endosomes and delivered to lysosomes for degradation. This is a highly regulated process that requires ubiquitination of cargo proteins as well as protein-sorting complexes that specifically recognize ubiquitinated cargo. Here, we show that IL-1beta induces ubiquitination of IL-1RI and that via these attached ubiquitin groups, IL-1RI interacts with the ubiquitin-binding protein Tollip. By using an assay to follow trafficking of IL-1RI from the cell surface to late endosomes and lysosomes, we demonstrate that Tollip is required for sorting of IL-1RI at late endosomes. In Tollip-deficient cells and cells expressing only mutated Tollip (incapable of binding IL-1RI and ubiquitin), IL-1RI accumulates on late endosomes and is not efficiently degraded. Furthermore, we show that IL-1RI interacts with Tom1, an ubiquitin-, clathrin-, and Tollip-binding protein, and that Tom1 knockdown also results in the accumulation of IL-1RI at late endosomes. Our findings suggest that Tollip functions as an endosomal adaptor linking IL-1RI, via Tom1, to the endosomal degradation machinery.
Sujets
PID Serval
serval:BIB_F91D88EA2918
PMID
Open Access
Oui
Date de création
2011-09-09T18:19:01.972Z
Date de création dans IRIS
2025-05-21T07:15:25Z