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KLHL12促进多巴胺受体D4.2和D4.4的非赖氨酸泛素化，但不促进与注意力缺陷多动障碍相关的D4.7变体的非赖氨酸泛素化。

KLHL12 Promotes Non-Lysine Ubiquitination of the Dopamine Receptors D4.2 and D4.4, but Not of the ADHD-Associated D4.7 Variant.

作者信息

Skieterska Kamila, Rondou Pieter, Lintermans Béatrice, Van Craenenbroeck Kathleen

机构信息

Laboratory of GPCR Expression and Signal Transduction (L-GEST), Ghent University, Ghent, Belgium.

出版信息

PLoS One. 2015 Dec 30;10(12):e0145654. doi: 10.1371/journal.pone.0145654. eCollection 2015.

DOI:10.1371/journal.pone.0145654
PMID:26717573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4738440/
Abstract

DOPAMINE D4 RECEPTOR POLYMORPHISM: The dopamine D4 receptor has an important polymorphism in its third intracellular loop that is intensively studied and has been associated with several abnormal conditions, among others, attention deficit hyperactivity disorder.

KLHL12 PROMOTES UBIQUITINATION OF THE DOPAMINE D4 RECEPTOR ON NON-LYSINE RESIDUES: In previous studies we have shown that KLHL12, a BTB-Kelch protein, specifically interacts with the polymorphic repeats of the dopamine D4 receptor and enhances its ubiquitination, which, however, has no influence on receptor degradation. In this study we provide evidence that KLHL12 promotes ubiquitination of the dopamine D4 receptor on non-lysine residues. By using lysine-deficient receptor mutants and chemical approaches we concluded that ubiquitination on cysteine, serine and/or threonine is possible.

DIFFERENTIAL UBIQUITINATION OF THE DOPAMINE D4 RECEPTOR POLYMORPHIC VARIANTS: Additionally, we show that the dopamine D4.7 receptor variant, which is associated with a predisposition to develop attention deficient hyperactivity disorder, is differentially ubiquitinated compared to the other common receptor variants D4.2 and D4.4. Together, our study suggests that GPCR ubiquitination is a complex and variable process.

摘要

多巴胺D4受体多态性：多巴胺D4受体在其第三个细胞内环中存在重要的多态性，该多态性受到深入研究，并且与多种异常情况相关，其中包括注意力缺陷多动障碍。

KLHL12促进多巴胺D4受体非赖氨酸残基的泛素化：在先前的研究中，我们已经表明，BTB-Kelch蛋白KLHL12与多巴胺D4受体的多态性重复序列特异性相互作用并增强其泛素化，然而，这对受体降解没有影响。在本研究中，我们提供证据表明KLHL12促进多巴胺D4受体非赖氨酸残基的泛素化。通过使用赖氨酸缺陷型受体突变体和化学方法，我们得出结论，半胱氨酸、丝氨酸和/或苏氨酸上的泛素化是可能的。

多巴胺D4受体多态性变体的差异泛素化：此外，我们表明，与注意力缺陷多动障碍易感性相关的多巴胺D4.7受体变体与其他常见受体变体D4.2和D4.4相比，存在差异泛素化。总之，我们的研究表明GPCR泛素化是一个复杂且可变的过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b1/4738440/891859657835/pone.0145654.g008.jpg
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