title: Activation of microtubule dynamics increases neuronal growth via the nerve growth factor (NGF)- and Gαs-mediated signaling pathways.
abstract: Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation.
authors.affiliation: From the Department of Physiology and Biophysics and.
authors.forename: Tulika
authors.initials: T
authors.lastname: Sarma
authors.affiliation: From the Department of Physiology and Biophysics and.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Koutsouris
authors.affiliation: From the Department of Physiology and Biophysics and.
authors.forename: Jiang Zhu
authors.initials: JZ
authors.lastname: Yu
authors.affiliation: From the Department of Physiology and Biophysics and Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Krbanjevic
authors.affiliation: the Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.affiliation: From the Department of Physiology and Biophysics and Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, the Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612 raz@uic.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rasenick
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D055495:Neurogenesis / Q000235:genetics; D016716:PC12 Cells; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D014404:Tubulin; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: G Protein; Growth Factor; Microtubule; Neurite Outgrowth; Neurotrophin