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

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)900-913
Number of pages14
JournalCellular Signalling
Publication statusPublished - 2010


  • GPCR
  • Dopamine
  • D4 receptor
  • KLHL12
  • Ubiquitination
  • Degradation
  • beta-arrestin2


Dive into the research topics of 'KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation'. Together they form a unique fingerprint.

Cite this