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

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• 作者：Markus Neumeier ; Sabrina Krautbauer ; S ; ra Schmidhofer ; Yvonne Hader ; Kristina Eisinger ; Elke Eggenhofer ; Stanley C. Froehner ; Marvin E. Adams ; Wolfgang Mages ; Christa Buechler
• 关键词：Adiponectin ; PDZ-protein ; Hepatocyte ; Syntrophin
• 刊名：Experimental and Molecular Pathology
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：95
• 期：2
• 页码：180-186
• 全文大小：740 K

文摘

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 ¦Â2-syntrophin (SNTB2). Hybridization of a PDZ-domain array with AdipoR1 C-terminal peptide shows association with PDZ-domains of further proteins including ¦Â1- and ¦Á-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.