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Characterization of intracellular translocation of Forkhead transcription factor O (FoxO) members induced by NGF in

Qiang Wen1, Xiaolu Duan, Rifang Liao

  • 1Neuropharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou, China.

Neuroscience Letters
|May 10, 2011
PubMed

Insights

Nerve growth factor (NGF) affects the nuclear translocation of Forkhead box O (FoxO) transcription factors differently in PC12 cells. FoxO1 and FoxO3a are excluded from the nucleus by NGF, while FoxO6 remains nuclear.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • Nuclear translocation of Forkhead transcription factors of the O class (FoxOs) is crucial for growth factor signaling.
  • The differential translocation properties of FOXO family members are not fully understood.

Purpose of the Study:

  • To investigate the effects of nerve growth factor (NGF) on the nuclear/cytoplasmic shuttling of FoxO1, FoxO3a, and FoxO6 in PC12 cells.
  • To determine the translocation kinetics and signaling pathways involved in NGF-induced FoxO nuclear exclusion.

Main Methods:

  • Utilized PC12 cell line expressing GFP-tagged FoxO proteins (FoxO1-GFP, FoxO3a-GFP, FoxO6-GFP).
  • Stimulated cells with NGF and analyzed protein localization using microscopy.
  • Investigated signaling pathways by applying inhibitors like K252a, LY294002, and PD98059.

Main Results:

  • NGF induced nuclear exclusion of FoxO1-GFP and FoxO3a-GFP in PC12 cells, but not FoxO6-GFP, which remained exclusively nuclear.
  • NGF-induced translocation was inhibited by K252a and LY294002, suggesting involvement of Trk and PI3K pathways.
  • FoxO3a exhibited faster cytoplasmic return and higher sensitivity to NGF stimulation compared to FoxO1.

Conclusions:

  • NGF differentially regulates the nuclear localization of FoxO1, FoxO3a, and FoxO6 in PC12 cells.
  • The differential responses of FoxO proteins to NGF highlight distinct roles in cellular signaling.
  • FoxO3a demonstrates a more dynamic response to NGF stimulation than FoxO1.

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