Dapper‐1 is essential for Wnt5a induced cardiomyocyte hypertrophy by regulating the Wnt/PCP pathway. Issue 14 (28th May 2014)

• Record Type: Journal Article
• Authors: Hagenmueller, Marco; Riffel, Johannes H.; Bernhold, Elmar; Fan, Jingjing; Katus, Hugo A.; Hardt, Stefan E.
• Is Part Of: FEBS letters. Volume 588:Issue 14(2014)
• Page Start: 2230
• Page End: 2237
• Publication Date: 2014-05-28
• Subjects: PCP -- planar cell polarity -- Vangl2 -- Van Gogh like 2 -- Cardiomyocyte hypertrophy -- Wnt Signaling; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.05.039
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : Wnt5a stimulation induces cardiomyocyte hypertrophy. Knockdown of Dpr1 blocks Wnt5a induced cardiomyocyte hypertrophy. Dpr1 is required for Wnt5a mediated activation of JNK. Dpr1 depletion leads to accumulation of Vangl2 in perinuclear located vesicles. Members of the Wnt/PCP pathway are upregulated in the remote area of the left ventricle in a rat myocardial infarction model.