On the track of function of KLHL12-mediated dopamine D4 receptor ubiquitination

Abstract

Event Abstract Back to Event On the track of function of KLHL12-mediated dopamine D4 receptor ubiquitination Kamila Skieterska1*, Pieter Rondou1, Dasiel O. Borroto-Escuela2, Dorien Clarisse1, Béatrice Lintermans1, Guy Haegeman1, Kjell Fuxe2 and Kathleen Van Craenenbroeck1 1 Ghent University, Physiology, Belgium 2 Karolinska Institutet, Neuroscience, Sweden The dopamine D4 receptor belongs to the superfamily of G protein-coupled receptors (GPCRs), the most common drug targets. The dopamine D4 gene displays a remarkable polymorphisms that differ in a variable number of tandem repeats in the region encoding the third intracellular loop. The most frequent variants in the human population are respectively: the 4-repeat allele (D4.4R), 7-repeat allele (D4.7R) and 2-repeat allele (D4.2R), of which the D4.7R polymorphic variant is associated with a predisposition to develop Attention Deficit Hyperactivity Disorder (ADHD). The functional role of the receptor polymorphic region is still poorly understood. We have identified a BTB-Kelch protein, KLHL12, which specifically interacts with the polymorphic repeats and enhances ubiquitination of the D4R. Interestingly, however, we have found that KLHL12 only marginally affects ubiquitination of the D4.7R variant, in contrast to strong induction of ubiquitination of the D4.2R and D4.4R variants. This suggests that differential ubiquitination of the D4R has functional implications. Most studies have focused on the role of GPCR ubiquitination in receptor degradation; nevertheless, our experimental results gave clear evidence that KLHL12-mediated D4R ubiquitination does not lead to receptor degradation. Moreover, our preliminary data suggest that KLHL12 might mediate a non-lysine ubiquitination of the receptor which is currently studied more profoundly. Furthermore, we are investigating the influence of ubiquitination on receptor signaling and found a role in modulation of cAMP level upon D4R activation. Acknowledgements This work was financially supported by FWO (Fonds voor Wetenschappelijk Onderzoek) Vlaanderen: project No. G.0109.09N. K. Skieterska is a recipient of a pre-doctoral FWO fellowship. K. Van Craenenbroeck has a post-doctoral FWO fellowship. Keywords: dopamine D4 receptor, Ubiquitination, KLHL12, ADHD, GPCR Conference: Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012. Presentation Type: Poster Presentation Topic: Other basic/clinical neurosciences topic Citation: Skieterska K, Rondou P, Borroto-Escuela DO, Clarisse D, Lintermans B, Haegeman G, Fuxe K and Van Craenenbroeck K (2012). On the track of function of KLHL12-mediated dopamine D4 receptor ubiquitination. Conference Abstract: Belgian Brain Council. doi: 10.3389/conf.fnhum.2012.210.00053 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Sep 2012; Published Online: 12 Sep 2012. * Correspondence: Ms. Kamila Skieterska, Ghent University, Physiology, Ghent, 9000, Belgium, kamila.skieterska@ugent.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck Google Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck Google Scholar Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck PubMed Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.