کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963742 1058496 2010 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation
چکیده انگلیسی

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 β-arrestin2 but this has no effect on the ubiquitination or localization of β-arrestin2 nor on the internalization of the D4 receptor.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 6, June 2010, Pages 900–913
نویسندگان
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