KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation

Pieter Rondou, Kamila Skieterska, Ann Packeu, Beatrice Lintermans, Peter Vanhoenacker, Georges Vauquelin, Guy Haegeman, Kathleen Van Craenenbroeck

Onderzoeksoutput: Articlepeer review

28 Citaten (Scopus)

Samenvatting

In previous studies, we identified KLHL12 as a novel interaction partner of the dopamine D4 receptor that functions as an adaptor in a Cul3-based E3 ubiquitin ligase complex to target the receptor for ubiquitination. In this study, we show that KLHL12 promotes poly-ubiquitination of the receptor by performing ubiquitination assays in eukaryotic cells. Furthermore, we demonstrate that KLHL12 not only interacts with both immature, ER-associated and mature, plasma membrane-associated D4 receptors, but also promotes ubiquitination of both receptor subpools. However, KLHL12 does not promote proteasomal degradation of newly synthesized receptors through the ER-associated degradation pathway or lysosomal degradation of mature receptors. Moreover, our data reveal that D4 receptors do not undergo agonist-promoted ubiquitination or degradation, in contrast to many other G-protein-coupled receptors (GPCRs). Together, our data show that KLHL12-mediated ubiquitination of the D4 receptor does not target the receptor for degradation, suggesting that D4 receptor ubiquitination, and maybe ubiquitination of GPCRs in general, might have alternative functions.
Originele taal-2English
Pagina's (van-tot)900-913
Aantal pagina's14
TijdschriftCellular Signalling
Volume22
StatusPublished - 2010

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