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Dopamine D2 receptor modulates Wnt expression and control of cell proliferation

Fei Han1,2, Prasad Konkalmatt1, Chaitanya Mokashi3

  • 1Department of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, USA.

Scientific Reports
|November 16, 2019
PubMed

Insights

Dopamine D2 receptor (D2R) signaling influences Wnt/β-catenin pathways by regulating Wnt3a expression. This cross-talk impacts cell proliferation and disease, offering new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Neuroscience

Background:

  • The Wnt/β-catenin pathway is crucial for development, cell proliferation, and disease, involving protein-level signaling and gene transcription.
  • Mechanisms controlling the expression and activity of the Wnt ligand Wnt3a are not well understood.

Purpose of the Study:

  • To investigate the cross-talk between dopamine D2 receptor (D2R) and Wnt/β-catenin signaling pathways.
  • To elucidate the role of D2R in modulating Wnt3a expression and its downstream effects.

Main Methods:

  • Analysis of Wnt3a promoter activity.
  • Investigation of D2R signaling effects on Wnt/β-catenin targets.
  • Assessment of D2R modulation of cell proliferation.
  • Evaluation in a renal ischemia/reperfusion injury model.

Main Results:

  • Evidence of significant cross-talk between D2R and Wnt/β-catenin signaling.
  • D2R signaling modulates Wnt3a expression via a conserved TCF/LEF site in the WNT3A promoter.
  • D2R signaling affects cell proliferation and renal injury pathology through Wnt/β-catenin pathways.

Conclusions:

  • Dopamine D2 receptor acts as a transcriptional modulator of Wnt/β-catenin signaling.
  • This interaction has broad implications for biological development and disease.
  • Findings suggest potential for new therapeutic strategies targeting D2R and Wnt signaling.

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