Intracellular trafficking of interleukin-1 receptor I requires Tollip.

Détails

ID Serval
serval:BIB_F91D88EA2918
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Intracellular trafficking of interleukin-1 receptor I requires Tollip.
Périodique
Current Biology
Auteur(s)
Brissoni B., Agostini L., Kropf M., Martinon F., Swoboda V., Lippens S., Everett H., Aebi N., Janssens S., Meylan E., Felberbaum-Corti M., Hirling H., Gruenberg J., Tschopp J., Burns K.
ISSN
0960-9822 (Print)
ISSN-L
0960-9822
Statut éditorial
Publié
Date de publication
2006
Volume
16
Numéro
22
Pages
2265-2270
Langue
anglais
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.
Mots-clé
Animals, Electrophoresis, Gel, Two-Dimensional, Endocytosis/physiology, Genetic Vectors/genetics, Humans, Immunoprecipitation, Interleukin-1beta/metabolism, Intracellular Signaling Peptides and Proteins/genetics, Intracellular Signaling Peptides and Proteins/metabolism, Mice, Microscopy, Fluorescence, Protein Transport/physiology, Proteins/genetics, Proteins/metabolism, Receptor, Epidermal Growth Factor/metabolism, Receptors, Interleukin-1 Type I/metabolism, Ubiquitin/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/09/2011 20:19
Dernière modification de la notice
09/05/2019 3:43
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