scholarly journals Heteromerization between α2A adrenoceptors and different polymorphic variants of the dopamine D4 receptor determines pharmacological and functional differences. Implications for impulsive-control disorders

2021 ◽  
pp. 105745
Author(s):  
Verònica Casadó-Anguera ◽  
Estefanía Moreno ◽  
Marta Sánchez-Soto ◽  
Ning Sheng Cai ◽  
Jordi Bonaventura ◽  
...  
2016 ◽  
Vol 44 (2) ◽  
pp. 601-605 ◽  
Author(s):  
Kamila Skieterska ◽  
Pieter Rondou ◽  
Kathleen Van Craenenbroeck

Ubiquitination is a post-translational modification that targets proteins for degradation but can also regulate other cellular processes such as endocytosis, trafficking and DNA repair. We investigate ubiquitination of the dopamine D4 receptor (D4R) which belongs to the superfamily of G protein-coupled receptors (GPCR). Several polymorphic variants of the D4R exist, which differ in the number of 16-amino acid repeats in the third intracellular loop (IC3) of the receptor. The functional role of this polymorphic region is not known but persons with the seven-repeat allele show a predisposition to develop attention deficit hyperactivity disorder (ADHD). We identified a protein, KLHL12, which specifically interacts with this polymorphic region and enhances ubiquitination of the D4R. We have tested the influence of KLHL12 on the ubiquitination of the most common D4R polymorphic variants and found that KLHL12 strongly promotes ubiquitination of the two- and four-repeat variant but has hardly any effect on ubiquitination of the seven-repeat D4R. This suggests that differential ubiquitination of the D4R may have functional implications. Moreover, we were able to demonstrate that KLHL12-mediated D4R ubiquitination does not lead to receptor degradation. Next, we aimed to identify specific residues in the sequence of D4R which undergo ubiquitination and observed that the lysine-less receptor mutant is still ubiquitinated. Subsequently, we have tested the hypothesis whether KLHL12 could promote ubiquitination on non-lysine residues of the D4R. The importance of the cysteine and serine/threonine residues in the ubiquitination process of the receptor was examined and the obtained results confirmed that D4R can be ubiquitinated on non-lysine residues. In this review we summarize our data on D4R ubiquitination and put this in the light of other GPCR ubiquitination studies.


2007 ◽  
Vol 562 (3) ◽  
pp. 165-173 ◽  
Author(s):  
Carolina Wedemeyer ◽  
Juan D. Goutman ◽  
María E. Avale ◽  
Lucía F. Franchini ◽  
Marcelo Rubinstein ◽  
...  

2021 ◽  
Vol 212 ◽  
pp. 113141
Author(s):  
Gianfabio Giorgioni ◽  
Fabio Del Bello ◽  
Pegi Pavletić ◽  
Wilma Quaglia ◽  
Luca Botticelli ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Catherine Paquet ◽  
Andre Krumel Portella ◽  
Spencer Moore ◽  
Yu Ma ◽  
Alain Dagher ◽  
...  

Abstract Background Evidence for the impact of the food retailing environment on food-related and obesity outcomes remains equivocal, but only a few studies have attempted to identify sub-populations for whom this relationship might be stronger than others. Genetic polymorphisms related to dopamine signalling have been associated with differences in responses to rewards such as food and may be candidate markers to identify such sub-populations. This study sought to investigate whether genetic variation of the dopamine D4 receptor gene (DRD4 exon III 48 bp VNTR polymorphism) moderated the association between local exposure to food retailers on BMI and diet in a sample of 4 to12-year-old children. Methods Data collected from a birth cohort and a community cross-sectional study conducted in Montreal, Canada, were combined to provide DRD4 VNTR polymorphism data in terms of presence of the 7-repeat allele (DRD4-7R) for 322 children aged between 4 and 12 (M (SD): 6.8(2.8) y). Outcomes were Body Mass Index (BMI) for age and energy density derived from a Food Frequency Questionnaire. Food environment was expressed as the proportion of local food retailers classified as healthful within 3 km of participants’ residence. Linear regression models adjusted for age, sex, income, cohort, and geographic clustering were used to test gene*environment interactions. Results A significant gene*food environment interaction was found for energy density with results indicating that DRD4-7R carriers had more energy dense diets than non-carriers, with this effect being more pronounced in children living in areas with proportionally more unhealthy food retailers. No evidence of main or interactive effects of DRD4 VNTR and food environment was found for BMI. Conclusions Results of the present study suggest that a genetic marker related to dopamine pathways can identify children with potentially greater responsiveness to unhealthy local food environment. Future studies should investigate additional elements of the food environment and test whether results hold across different populations.


2012 ◽  
Vol 18 (4) ◽  
pp. 402-403 ◽  
Author(s):  
K Anacker ◽  
S Enge ◽  
A Reif ◽  
K-P Lesch ◽  
A Strobel

2004 ◽  
Vol 126B (1) ◽  
pp. 74-78 ◽  
Author(s):  
Z. Ronai ◽  
E. Szantai ◽  
R. Szmola ◽  
Z. Nemoda ◽  
A. Szekely ◽  
...  

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