title: Tankyrase-mediated β-catenin activity regulates vasopressin-induced AQP2 expression in kidney collecting duct mpkCCDc14 cells.
abstract: Aquaporin-2 (AQP2) mediates arginine vasopressin (AVP)-induced water reabsorption in the kidney collecting duct. AVP regulates AQP2 expression primarily via Gsα/cAMP/PKA signaling. Tankyrase, a member of the poly(ADP-ribose) polymerase family, is known to mediate Wnt/β-catenin signaling-induced gene expression. We examined whether tankyrase plays a role in AVP-induced AQP2 regulation via ADP-ribosylation of G protein-α (Gα) and/or β-catenin-mediated transcription of AQP2. RT-PCR and immunoblotting analysis revealed the mRNA and protein expression of tankyrase in mouse kidney and mouse collecting duct mpkCCDc14 cells. dDAVP-induced AQP2 upregulation was attenuated in mpkCCDc14 cells under the tankyrase inhibition by XAV939 treatment or small interfering (si) RNA knockdown. Fluorescence resonance energy transfer image analysis, however, revealed that XAV939 treatment did not affect dDAVP- or forskolin-induced PKA activation. Inhibition of tankyrase decreased dDAVP-induced phosphorylation of β-catenin (S552) and nuclear translocation of phospho-β-catenin. siRNA-mediated knockdown of β-catenin decreased forskolin-induced AQP2 transcription and dDAVP-induced AQP2 expression. Moreover, inhibition of phosphoinositide 3-kinase/Akt, which was associated with decreased nuclear translocation of β-catenin, diminished dDAVP-induced AQP2 upregulation, further indicating that β-catenin mediates AQP2 expression. Taken together, tankyrase plays a role in AVP-induced AQP2 regulation, which is likely via β-catenin-mediated transcription of AQP2, but not ADP-ribosylation of Gα. The results provide novel insights into vasopressin-mediated urine concentration and homeostasis of body water metabolism.
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, South Korea;
authors.forename: Hyun Jun
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, South Korea;
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, South Korea;
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, South Korea;
authors.forename: Eui-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, South Korea;
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Lim
authors.affiliation: The Water and Salt Research Center, Department of Biomedicine, Aarhus University, Aarhus C, Denmark; and.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
authors.affiliation: The Water and Salt Research Center, Department of Biomedicine, Aarhus University, Aarhus C, Denmark; and Institute of Medicine and Health Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, South Korea; thkwon@knu.ac.kr.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006706:Homeostasis; D007150:Immunohistochemistry; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D038501:Tankyrases / Q000378:metabolism*; D015854:Up-Regulation; D014667:Vasopressins; D014867:Water / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; C495267:CTNNB1 protein, mouse; D044385:GTP-Binding Protein alpha Subunits; D051176:beta Catenin; D014867:Water; D014667:Vasopressins; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D000242:Cyclic AMP; D038501:Tankyrases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3
keywords: aquaporin-2; collecting duct; tankyrase; vasopressin; β-catenin