Dapper-1 is essential for Wnt5a induced cardiomyocyte hypertrophy by regulating the Wnt/PCP pathway

FEBS Lett. 2014 Jun 27;588(14):2230-7. doi: 10.1016/j.febslet.2014.05.039. Epub 2014 May 28.

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.

Keywords: Cardiomyocyte hypertrophy; Wnt Signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / metabolism
  • Cell Size
  • Cells, Cultured
  • Cytoplasmic Vesicles / metabolism
  • MAP Kinase Signaling System
  • Myocardial Infarction / metabolism
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Myocytes, Cardiac / physiology
  • Nuclear Proteins / physiology*
  • Protein Transport
  • Rats
  • Rats, Wistar
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway*
  • Wnt-5a Protein

Substances

  • Dact1 protein, rat
  • Nuclear Proteins
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, rat