4.7 Article

Functional Characterization of the Obesity-Linked Variant of the beta(3)-Adrenergic Receptor

期刊

出版社

MDPI
DOI: 10.3390/ijms22115721

关键词

G-protein coupled receptors; beta-3-adrenergic receptor; receptor desensitization

资金

  1. King Abdullah International Medical Research Center (KAIMRC) [RC13/268/R]

向作者/读者索取更多资源

ADR beta(3) is a crucial receptor involved in lipid metabolism regulation, with a genetic variant W64R linked to diabetes and obesity, showing no significant functional differences compared to the wild-type counterpart.
Adrenergic receptor beta(3) (ADR beta(3)) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADR beta(3) activates adenylate cyclase and increases cAMP in the cells. ADR beta(3) is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADR beta(3) is associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADR beta(3). This study was initiated to functionally characterize this obesity-linked variant of ADR beta(3). We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADR beta(3) using single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADR beta(3) shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike adrenergic receptor beta(2) (ADR beta(2)), agonist-induced desensitization of ADR beta(3) does not involve loss of cell surface expression. WT and W64R variant of ADR beta(3) displayed comparable biochemical properties, and there was no significant impact of the substitution of tryptophan with arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADR beta(3). The obesity-linked W64R variant of ADR beta(3) is indistinguishable from the WT ADR beta(3) in terms of expression, cellular distribution, signaling, and post-activation behavior.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据