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Editorial
. 2014 Jan 31;114(3):402-5.
doi: 10.1161/CIRCRESAHA.113.303114.

Hippo activation in arrhythmogenic cardiomyopathy

Yong Hu  1 , William T Pu
Affiliations
Editorial

Hippo activation in arrhythmogenic cardiomyopathy

Yong Hu et al. Circ Res. .
No abstract available

Keywords: Editorials; Hippo protein, human; YAP protein, mouse; arrhythmogenic right ventricular cardiomyopathy; desmosomes.

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Figures

Figure
Figure. Potential interaction of Hippo/YAP and Wnt/β-catenin signaling pathways in arrhythmogenic cardiomyopathy (AC)
Top panel shows normal myocardial intercalated disk (ID), containing desmosomes (DSG2/DSC2/PKP2/PG/DSP) and adhesion junctions (CDH2/β-catenin/α-catenin). The intact ID retains PKCα near the membrane, leading to phosphorylation and inactivation of NF2 (i). YAP phosphorylation state is low, and PG is bound to desmosomes and localized at the ID (ii). Wnt/β-catenin signaling can proceed normally (iii). Bottom panel shows disruption of the ID in AC by a desmosomal mutation (e.g. in PKP2; iv). ID disruption causes both loss of mechanical integrity and aberrant signaling. Loss of PKCα sub-membrane localization activates NF2 and the Hippo kinase cascade (MST and LATS; v). As a result, YAP is phosphorylated and localizes to IDs, perhaps by binding to α-catenin (vi). Phosphorylated TAZ may also bind to Dvl and thereby activate APC to enhance β-catenin degradation (vii). Nuclear PG, perhaps in the form of a complex with β-catenin and YAP, interferes with nuclear β-catenin and possible YAP transcriptional activity (viii). This complex may also have non-transcriptional roles in the cytoplasm or near IDs.
See this image and copyright information in PMC

Comment on

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