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Heterotrimeric G‐proteins associate with microtubules during differentiation in PC12 pheochromocytoma cells
Author(s) -
Sarma Tulika,
Voyno-Yasenetskaya Tatyana,
Hope Thomas J.,
Rasenick Mark M.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0730com
Subject(s) - microbiology and biotechnology , nocodazole , heterotrimeric g protein , microtubule , biology , g protein , neurite , cytoskeleton , signal transduction , chemistry , cell , biochemistry , in vitro
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 G αs , G αi1 , and G αo 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 G α association with microtubules that was coincident with the extension of “neurites.” There were distinctions among the G α subtypes, with G αs showing the most profound NGF‐induced colocalization with tubulin. Translocation of G α 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, G α 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.—Sarma, T., Voyno‐Yasenetskaya, T., Hope, T. J., Rasenick, M. M. Heterotrimeric G‐proteins associate with microtubules during differentiation in PC12 pheochromocytoma cells. FASEB J. 17, 848–859 (2003)