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GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling

Ekaterina Posokhova1, Animesh Shukla1, Steven Seaman1

  • 1Tumor Angiogenesis Section, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI) at Frederick, National Institutes of Health (NIH), Frederick, MD 21702, USA.

Cell Reports
|January 6, 2015
PubMed

Insights

G protein-coupled receptor 124 (GPR124) is crucial for brain blood vessel development. It acts as a WNT7A/WNT7B-specific costimulator, enhancing beta-catenin signaling in brain endothelial cells for proper angiogenesis and blood-brain barrier formation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • G protein-coupled receptor 124 (GPR124) is an adhesion GPCR involved in CNS angiogenesis and blood-brain barriergenesis.
  • Previous studies showed Gpr124 disruption causes developmental defects, similar to Wnt7a/Wnt7b or beta-catenin deletion in endothelial cells, suggesting a link to WNT signaling.

Purpose of the Study:

  • To investigate the functional relationship between GPR124 and canonical WNT signaling in brain endothelium.
  • To elucidate the role of GPR124 in CNS angiogenesis and blood-brain barrier formation.

Main Methods:

  • In vitro reporter assays to assess signaling.
  • Mutation analysis to identify key GPR124 domains.
  • In vivo genetic interaction studies in mice.

Main Results:

  • GPR124 acts as a WNT7A/WNT7B-specific costimulator of beta-catenin signaling in brain endothelial cells.
  • WNT7-stimulated beta-catenin signaling requires GPR124's intracellular PDZ binding motif and extracellular leucine-rich repeats.
  • GPR124 is vital for potentiating WNT7-induced canonical beta-catenin signaling.

Conclusions:

  • GPR124 plays a critical role in enhancing WNT7-mediated beta-catenin signaling in the brain endothelium.
  • Understanding GPR124's function is key for manipulating CNS angiogenesis and blood-brain barriergenesis.

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