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Nuclear localization of Formyl-Peptide Receptor 2 in human cancer cells

Fabio Cattaneo1, Melania Parisi1, Tiziana Fioretti2

  • 1Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy.

Archives of Biochemistry and Biophysics
|May 15, 2016
PubMed

Insights

Nuclear formyl-peptide receptor 2 (FPR2) signals within the nucleus, regulating distinct cascades. Its nuclear localization depends on specific residues within its nuclear localization sequence (NLS).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • G protein-coupled receptors (GPCRs) traditionally signal from the cell surface.
  • Emerging evidence shows GPCRs, including formyl-peptide receptor 2 (FPR2), also function within the nucleus.
  • Nuclear FPR2 signaling regulates distinct intracellular pathways.

Purpose of the Study:

  • To investigate the nuclear localization and function of FPR2.
  • To identify the nuclear localization sequence (NLS) responsible for FPR2 nuclear import.
  • To determine the role of specific amino acid residues in FPR2 nuclear translocation.

Main Methods:

  • Western blot analysis and immunofluorescence to detect nuclear FPR2 expression.
  • Radioligand binding assays to assess receptor function.
  • Site-directed mutagenesis to analyze the FPR2 NLS and its functional impact.

Main Results:

  • FPR2 is expressed at the nuclear level in CaLu-6 and AGS cells.
  • Nuclear FPR2 is functional, mediating intracellular signaling including G protein dissociation and phosphorylation of ERK2, c-Jun, and c-Myc upon agonist stimulation.
  • A nuclear localization sequence (NLS) containing basic amino acids (227-KIHKK-231) was identified in FPR2.
  • Mutagenesis studies revealed that the integrity of H(229) and K(231) residues within the NLS is crucial for FPR2 nuclear localization.

Conclusions:

  • FPR2 exhibits functional signaling within the nucleus.
  • The identified NLS is essential for FPR2 nuclear translocation.
  • Specific residues H(229) and K(231) within the NLS are critical for FPR2 nuclear import, highlighting a novel mechanism for GPCR nuclear function.
Keywords:
FPR2G protein-coupled receptorsNuclear localizationSignal transduction

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