Adiponectin receptor 1 C-terminus interacts with PDZ-domain proteins such as syntrophins.

Adiponectin receptor 1 C-terminus interacts with PDZ-domain proteins such as syntrophins.
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DOI:
10.1016/j.yexmp.2013.07.002
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发表时间:
2013-10
影响因子:
3.6
通讯作者:
Buechler, Christa
Buechler, Christa
中科院分区:
医学3区
文献类型:
--
作者:
Neumeier, Markus;Krautbauer, Sabrina;Schmidhofer, Sandra;Hader, Yvonne;Eisinger, Kristina;Eggenhofer, Elke;Froehner, Stanley C.;Adams, Marvin E.;Mages, Wolfgang;Buechler, Christa

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脂联素受体1 (AdipoR1)是脂联素的两个信号受体之一,在代谢性疾病中具有多种有益作用。AdipoR1 c端肽与I类PSD-95、disc large、ZO-1 (PDZ)蛋白的一致序列一致,并通过筛选肝酵母两种杂交文库鉴定其与β2-syntrophin (SNTB2)结合。PDZ结构域阵列与AdipoR1 c端肽的杂交显示与βl和α-syntrophin (SNTA)等其他蛋白质的PDZ结构域相关。PDZ蛋白与c端肽的相互作用需要在PDZ结合区旁边有一个游离的羧基末端,并被羧基末端添加的标签阻断。n末端标记的AdipoR1比c末端标记的受体表达更高,这表明游离羧基末端可能与PDZ蛋白形成复合物来调节细胞AdipoR1的水平。c端和n端标记的AdipoR1蛋白主要定位于细胞质中。在脂联素培养的Huh7细胞中,n端而非c端标记的AdipoR1与合营养素共定位。然而,在SNTA和SNTB2缺陷小鼠中,脂联素诱导的作为AdipoR1靶点的AMPK和p38 MAPK的肝脏磷酸化并未被阻断。此外,当被喂食标准食物或高脂肪食物时,AdipoR1蛋白在基因敲除型和野生型小鼠的肝脏中同样丰富。综上所述,这些数据表明AdipoR1蛋白水平是由迄今为止尚未表征的I类PDZ蛋白调控的,这与SNTA和SNTB2不同。
Adiponectin receptor 1 (AdipoR1) is one of the two signalling 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 βl-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.
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发表时间: 1995-05-23
期刊: BIOCHEMISTRY
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发表时间: 2009-02-10
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