Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
Exp Mol Pathol. 2013 Oct;95(2):180-6. doi: 10.1016/j.yexmp.2013.07.002. Epub 2013 Jul 13.
Adiponectin receptor 1 (AdipoR1) is one of the two signaling receptors of adiponectin with multiple beneficial effects in metabolic diseases. AdipoR1 C-terminal peptide is concordant with the consensus sequence of class I PSD-95, disc large, ZO-1 (PDZ) proteins, and screening of a liver yeast two hybrid library identified binding to β2-syntrophin (SNTB2). Hybridization of a PDZ-domain array with AdipoR1 C-terminal peptide shows association with PDZ-domains of further proteins including β1- and α-syntrophin (SNTA). Interaction of PDZ proteins and C-terminal peptides requires a free carboxy terminus next to the PDZ-binding region and is blocked by carboxy terminal added tags. N-terminal tagged AdipoR1 is more highly expressed than C-terminal tagged receptor suggesting that the free carboxy terminus may form a complex with PDZ proteins to regulate cellular AdipoR1 levels. The C- and N-terminal tagged AdipoR1 proteins are mainly localized in the cytoplasma. N-terminal but not C-terminal tagged AdipoR1 colocalizes with syntrophins in adiponectin incubated Huh7 cells. Adiponectin induced hepatic phosphorylation of AMPK and p38 MAPK which are targets of AdipoR1 is, however, not blocked in SNTA and SNTB2 deficient mice. Further, AdipoR1 protein is similarly abundant in the liver of knock-out and wild type mice when kept on a standard chow or a high fat diet. In summary these data suggest that AdipoR1 protein levels are regulated by so far uncharacterized class I PDZ proteins which are distinct from SNTA and SNTB2.
脂联素受体 1（AdipoR1）是脂联素的两种信号受体之一，在代谢性疾病中具有多种有益作用。AdipoR1 C 端肽与 PSD-95、Disc large、ZO-1（PDZ）蛋白的 I 类共识序列一致，通过筛选肝酵母双杂交文库，发现与β2-肌联蛋白（SNTB2）结合。PDZ 结构域阵列与 AdipoR1 C 端肽的杂交显示与包括β1-和α-肌联蛋白（SNTA）在内的进一步蛋白质的 PDZ 结构域相关联。PDZ 蛋白和 C 端肽的相互作用需要 PDZ 结合区旁边的游离羧基末端，并且被羧基末端添加的标签阻断。与 C 端标签相比，N 端标签的 AdipoR1 表达更高，表明游离羧基末端可能与 PDZ 蛋白形成复合物，以调节细胞内 AdipoR1 水平。C 端和 N 端标签的 AdipoR1 蛋白主要定位于细胞质中。N 端但不是 C 端标签的 AdipoR1 与在脂联素孵育的 Huh7 细胞中的肌联蛋白共定位。然而，在 SNTA 和 SNTB2 缺陷小鼠中，脂联素诱导的 AMPK 和 p38 MAPK 的肝磷酸化不受阻断，后者是 AdipoR1 的靶点。此外，当用标准饲料或高脂肪饮食喂养时，AdipoR1 蛋白在敲除和野生型小鼠的肝脏中的丰度相似。总之，这些数据表明 AdipoR1 蛋白水平受到迄今为止尚未表征的 I 类 PDZ 蛋白的调节，这些蛋白与 SNTA 和 SNTB2 不同。
