title: Dapper-1 is essential for Wnt5a induced cardiomyocyte hypertrophy by regulating the Wnt/PCP pathway.
abstract: The Wnt signaling pathway was identified as crucial mediator of cardiomyocyte hypertrophy. In this study we found that activation of non-canonical Wnt signaling by Wnt5a stimulates protein synthesis and enlargement of cardiomyocyte surface area. These hypertrophic features were inhibited in Dapper-1 (Dpr1) depleted cells. On the molecular level, we observed inhibition of the non-canonical Wnt/planar-cell-polarity (PCP) pathway denoted by reduction of c-jun-n-terminal-kinase (JNK) phosphorylation. Upstream of JNK, increased protein levels of the Wnt/PCP trans-membrane receptor van-Gogh-like-2 (Vangl2) were observed along with an enrichment of Vangl2 in perinuclear located vesicles. The findings suggest that Dpr1 is essential for execution of the Wnt/PCP pathway and regulation of the Vangl2/JNK axis. Depletion of Dpr1 inhibits non-canonical Wnt signaling induced cardiomyocyte hypertrophy by blocking Wnt/PCP signaling.
authors.affiliation: Department of Cardiology, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Hagenmueller
authors.affiliation: Department of Cardiology, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Riffel
authors.affiliation: Department of Cardiology, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Bernhold
authors.affiliation: Department of Cardiology, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Cardiology, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany. Electronic address: stefan.hardt@med.uni-heidelberg.de.
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Hardt
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009203:Myocardial Infarction / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein
chemical_list: C503247:Dact1 protein, rat; D009687:Nuclear Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat
keywords: Cardiomyocyte hypertrophy; Wnt Signaling