title: Adiponectin receptor 1 C-terminus interacts with PDZ-domain proteins such as syntrophins.
abstract: 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.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Neumeier
authors.forename: Sabrina
authors.initials: S
authors.lastname: Krautbauer
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmidhofer
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hader
authors.forename: Kristina
authors.initials: K
authors.lastname: Eisinger
authors.forename: Elke
authors.initials: E
authors.lastname: Eggenhofer
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Froehner
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Adams
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mages
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002460:Cell Line; D049029:Dystrophin-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054731:PDZ Domains; D011494:Protein Kinases / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; D049029:Dystrophin-Associated Proteins; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C091824:syntrophin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases
keywords: Adiponectin; Hepatocyte; PDZ-protein; Syntrophin