KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation.
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Rondou P, Skieterska K, Packeu A, Lintermans B, Vanhoenacker P, Vauquelin G, Haegeman G, Van Craenenbroeck K
KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation.
Cell Signal. 2010 Jun;22(6):900-13. doi: 10.1016/j.cellsig.2010.01.014. Epub 2010 Jan 25.
- PubMed ID
- 20100572 [ View in PubMed]
- Abstract
In previous studies, we identified KLHL12 as a novel interaction partner of the dopamine D4 receptor that functions as an adaptor in a Cullin3-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. Unexpectedly, however, KLHL12-mediated receptor ubiquitination 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) indicating that ubiquitination of GPCRs does not defaultly lead to receptor degradation. Interestingly, KLHL12 does also interact with beta-arrestin2 but this has no effect on the ubiquitination or localization of beta-arrestin2 nor on the internalization of the D4 receptor.