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

作者：Hagenmueller Marco; Riffel Johannes H; Bernhold Elmar; Fan Jingjing; Katus Hugo A; Hardt Stefan E^*

来源：FEBS LETTERS, 2014, 588(14): 2230-2237.

DOI：10.1016/j.febslet.2014.05.039

• Cardiomyocyte hypertrophy
• Wnt Signaling

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 (Vang12) were observed along with an enrichment of Vang12 in perinuclear located vesicles. The findings suggest that Dpr1 is essential for execution of the Wnt/PCP pathway and regulation of the Vang12/INK axis. Depletion of Dpr1 inhibits non-canonical Wnt signaling induced cardiomyocyte hypertrophy by blocking Wnt/PCP signaling.
Structured summary of protein

• 出版日期2014-6-27