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Heterotrimeric G-proteins associate with microtubules during differentiation in PC12 pheochromocytoma cells

Tulika Sarma1, Tatyana Voyno-Yasenetskaya, Thomas J Hope

  • 1Department of Physiology, College of Medicine, Chicago, Illinois 60612-7342, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 2, 2003
PubMed

Insights

Nerve growth factor (NGF) signaling triggers the relocation of specific G-proteins (Galpha subunits) to cellular processes, associating with tubulin structures. This G-protein movement is crucial for neuronal differentiation and cytoskeletal rearrangement.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • Tubulin influences G-protein signaling, and G-proteins regulate microtubule assembly.
  • G-protein-coupled receptors and receptor tyrosine kinases interact in cellular signaling pathways.

Purpose of the Study:

  • To investigate the interplay between G-protein signaling and cytoskeletal dynamics during neuronal differentiation.
  • To determine the role of G-protein translocation in response to nerve growth factor (NGF) in PC12 cells.

Main Methods:

  • Utilized PC12 pheochromocytoma and Neuro-2A cells.
  • Employed nocodazole and latrunculin to assess microtubule and actin involvement.
  • Applied deconvolution microscopy and immunoprecipitation to analyze Galpha-microtubule association.
  • Investigated the impact of MAP kinase inhibitors on G-protein translocation.

Main Results:

  • NGF signaling induced translocation of Galpha(s), Galpha(i1), and Galpha(o) to cellular processes, co-localizing with tubulin.
  • Microtubule integrity was essential for this G-protein relocation; nocodazole blocked and reversed it, while latrunculin had no effect.
  • Galpha association with microtubules increased significantly during neurite extension.
  • Galpha(s) showed the most pronounced NGF-induced colocalization with tubulin.
  • G-protein translocation was inhibited by agents blocking MAP kinases required for neuronal differentiation.
  • Similar Galpha translocation was observed in spontaneously differentiating Neuro-2A cells.

Conclusions:

  • Neuronal differentiation signals trigger G-protein relocation, suggesting a role in cytoskeletal rearrangement.
  • Specific G-proteins may mediate diverse signals that promote neuronal differentiation and morphological changes.
  • The interplay between G-protein signaling and microtubules is critical for neuronal development.

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