Orphan G protein-coupled receptor GPRC5A modulates integrin β1-mediated epithelial cell adhesion

Daria R Bulanova1, Yevhen A Akimov1, Anne Rokka2

  • 1a Institute for Molecular Medicine Finland (FIMM), University of Helsinki , Helsinki , Finland.

Insights

G-Protein Coupled Receptor Class C Group 5 Member A (GPRC5A) is crucial for cell adhesion and downstream signaling. Its depletion impairs integrin-mediated cell adhesion, suggesting a role in epithelial cancers.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • G-Protein Coupled Receptor Class C Group 5 Member A (GPRC5A) is linked to various cancers.
  • Mechanisms of GPRC5A's role in cancer are not well understood.

Purpose of the Study:

  • To investigate the function of GPRC5A in cell adhesion and signaling pathways.
  • To explore the interaction of GPRC5A with other cellular components.

Main Methods:

  • CRISPR/Cas9 gene knockout and RNA interference (RNAi) in human cell lines.
  • Assessment of cell adhesion to extracellular matrix proteins (collagens, fibronectin, Matrigel).
  • Analysis of integrin β1 (ITGB1) expression, focal adhesion kinase (FAK) phosphorylation, and small GTPase activity (RhoA, Rac1).
  • Investigation of GPRC5A interaction with EphA2 receptor tyrosine kinase.

Main Results:

  • GPRC5A knockout/depletion significantly reduced cell adhesion to integrin substrates and Matrigel.
  • GPRC5A deficiency correlated with decreased ITGB1 expression, impaired FAK phosphorylation, and reduced RhoA/Rac1 activity.
  • A direct interaction between GPRC5A and EphA2 was identified, though its functional impact on adhesion is unclear.

Conclusions:

  • GPRC5A plays a critical role in regulating ITGB1-mediated cell adhesion and associated signaling pathways.
  • GPRC5A's function in cell adhesion suggests a potential novel role in the development of human epithelial cancers.

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