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

Tulika Sarma, Tatyana Voyno-Yasenetskaya, Thomas J. Hope, Mark M. Rasenick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Tubulin modifies G-protein signaling and heterotrimeric G-proteins regulate microtubule assembly. Here we report an interplay among G-protein-coupled receptor and receptor tyrosine kinase (such as nerve growth factor-NGF) signaling systems in PC12 pheochromocytoma cells that resulted in a translocation of Gαs, Gαi1, and Gαo from cell bodies to cellular processes where they appear to localize with tubulin-containing structures. This relocation appeared to depend on the integrity of microtubules, as it was blocked and reversed by nocodazole. Latrunculin, which promotes actin filament depolymerization, had no effect. Both deconvolution microscopy and immunoprecipitation showed a significant increase of Gα association with microtubules that was coincident with the extension of "neurites." There were distinctions among the Gα subtypes, with Gαs showing the most profound NGF-induced colocalization with tubulin. Translocation of Gα was blocked by agents that inhibit the MAP kinases required for neuronal differentiation, suggesting that G-protein relocation is triggered by the intracellular signals for differentiation. Consistent with this, Gα in Neuro-2A cells, which spontaneously differentiate, showed a similar translocation coincident with differentiation. Thus, diverse signals that promote neuronal differentiation and changes in cell morphology may use specific G-proteins to evoke cytoskeletal rearrangement.

Original languageEnglish (US)
Pages (from-to)848-859
Number of pages12
JournalFASEB Journal
Volume17
Issue number8
DOIs
StatePublished - May 2003

Keywords

  • Cytoskeleton
  • G-protein
  • Growth cone
  • NGF
  • Tubulin

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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