Dopamine D Receptor Modulates Wnt Expression and Control of Cell Proliferation

Overview

Journal Sci Rep

Specialty Science

Date 2019 Nov 16

PMID 31727925

Citations 15

Authors

Fei Han

Prasad Konkalmatt

Chaitanya Mokashi

Megha Kumar

Yanrong Zhang

Allen Ko

Zachary J Farino

Laureano D Asico

Gaosi Xu

John Gildea

Xiaoxu Zheng

Robin A Felder

Robin E C Lee

Pedro A Jose

Zachary Freyberg

Ines Armando

Affiliations

Soon will be listed here.

Abstract

The Wnt/β-catenin pathway is one of the most conserved signaling pathways across species with essential roles in development, cell proliferation, and disease. Wnt signaling occurs at the protein level and via β-catenin-mediated transcription of target genes. However, little is known about the underlying mechanisms regulating the expression of the key Wnt ligand Wnt3a or the modulation of its activity. Here, we provide evidence that there is significant cross-talk between the dopamine D receptor (D2R) and Wnt/β-catenin signaling pathways. Our data suggest that D2R-dependent cross-talk modulates Wnt3a expression via an evolutionarily-conserved TCF/LEF site within the WNT3A promoter. Moreover, D2R signaling also modulates cell proliferation and modifies the pathology in a renal ischemia/reperfusion-injury disease model, via its effects on Wnt/β-catenin signaling. Together, our results suggest that D2R is a transcriptional modulator of Wnt/β-catenin signal transduction with broad implications for health and development of new therapeutics.

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