Nuclear G protein signaling: new tricks for old dogs

Rhiannon Campden1, Nicolas Audet, Terence E Hébert

  • 1Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada.

Insights

G protein-coupled receptors (GPCRs) and G proteins function within the nucleus, not just the cell membrane. Nuclear signaling pathways impact cellular functions, including in heart cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cardiology

Background:

  • The standard model places G protein-coupled receptors (GPCRs) exclusively on the cell membrane.
  • This model does not account for GPCRs, G proteins, and signaling molecules found within the nucleus.
  • Emerging evidence highlights nuclear localization and function of these signaling components.

Purpose of the Study:

  • To review the presence and function of G proteins within the nucleus.
  • To explore nuclear G protein-dependent signaling pathways.
  • To emphasize cardiac signaling implications of nuclear G proteins.

Main Methods:

  • Review of existing literature on nuclear GPCRs and G proteins.
  • Analysis of evidence from isolated nuclei studies.
  • Focus on G protein signaling pathways in cardiomyocytes.

Main Results:

  • GPCRs are present on the nuclear membrane and can activate G protein signaling pathways within the nucleus.
  • Nuclear G protein pathways can mimic cell surface signaling, including cyclic adenosine monophosphate, calcium, and nitric oxide synthase activation.
  • Various heterotrimeric and monomeric G proteins are identified in the nucleus across different cell types.

Conclusions:

  • The function of GPCRs and G proteins extends beyond the cell membrane to the nucleus.
  • Nuclear G protein signaling plays a role in cellular processes, particularly evident in cardiac cells.
  • Further research into nuclear G protein function is warranted.

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