Tubulin stimulates adenylyl cyclase activity in C6 glioma cells by bypassing the beta-adrenergic receptor: a potential mechanism of G protein activation.

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  • Author(s): Yan K;Yan K; Popova JS; Moss A; Shah B; Rasenick MM
  • Source:
    Journal of neurochemistry [J Neurochem] 2001 Jan; Vol. 76 (1), pp. 182-90.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print Cited Medium: Print ISSN: 0022-3042 (Print) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE
    • Publication Information:
      Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
      Original Publication: New York : Raven Press
    • Subject Terms:
      Adenylyl Cyclases/*metabolism ; GTP-Binding Proteins/*metabolism ; Glioma/*metabolism ; Guanosine Triphosphate/*analogs & derivatives ; Receptors, Adrenergic, beta/*metabolism ; Tubulin/*metabolism; Adrenergic beta-Agonists/pharmacology ; Animals ; Azides/metabolism ; Cell Membrane/metabolism ; Cell Membrane Permeability/drug effects ; Enzyme Activation/drug effects ; GTP-Binding Protein alpha Subunits, Gs/drug effects ; GTP-Binding Protein alpha Subunits, Gs/metabolism ; Guanosine Triphosphate/metabolism ; Guanylyl Imidodiphosphate/pharmacology ; Precipitin Tests ; Rats ; Saponins/pharmacology ; Signal Transduction/drug effects ; Tubulin/pharmacology ; Tumor Cells, Cultured
    • Abstract:
      While the cytoskeleton is known to play several roles in the biology of the cell, one role, which has been revealed only recently, is that of a participant in the signal transduction process. Tubulin binds specifically to the alpha subunits of Gs (stimulatory GTP-binding regulatory protein of adenylyl cyclase), Gi1 (inhibitory protein of adenylyl cyclase), and Gq and transactivates those molecules through direct transfer of GTP. The relevance of this transactivation process to G proteins which are normally activated by a neurotransmitter-occupied receptor is the subject of this study. C6 glioma cells, made permeable with saponin, retained tight coupling between Gs and the beta-adrenergic receptor. Although 5-guanylylimidodiphosphate (GppNHp) was incapable of activating Gs (and subsequently, adenylyl cyclase) in the absence of agonist, tubulin with GppNHp bound (tubulin-GppNHp) activated adenylyl cyclase with an EC(50) of 30 nM. Desensitization of beta-adrenergic receptors by isoproterenol exposure had no effect on the ability of tubulin-GppNHp to activate Gs and adenylyl cyclase. When the photoaffinity GTP analog, azidoanilido GTP (AAGTP; P3(4-azidoanilido)-P1-5'-GTP), was added to C6 membranes or permeable C6 cells, it was only weakly incorporated by G alpha s in the absence of isoproterenol. When the same concentration of dimeric tubulin with AAGTP bound was introduced, AAGTP was transferred from tubulin to G alpha s, activating the latter species. Similar 'preferential' activation of G alpha s by tubulin-AAGTP versus the free nucleotide was seen using purified components. Thus, membrane-associated tubulin may serve to activate G alpha s, independent of signals not normally coupled to that protein. Tubulin may act as an agent to link a variety of membrane-associated signalling systems.
    • Grant Information:
      AG 15482 United States AG NIA NIH HHS; MH 57391 United States MH NIMH NIH HHS
    • Accession Number:
      0 (Adrenergic beta-Agonists)
      0 (Azides)
      0 (Receptors, Adrenergic, beta)
      0 (Saponins)
      0 (Tubulin)
      34273-04-6 (Guanylyl Imidodiphosphate)
      60869-76-3 (GTP gamma-4-azidoanilide)
      86-01-1 (Guanosine Triphosphate)
      EC 3.6.1.- (GTP-Binding Proteins)
      EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
      EC 4.6.1.1 (Adenylyl Cyclases)
    • Publication Date:
      Date Created: 20010109 Date Completed: 20010208 Latest Revision: 20190630
    • Publication Date:
      20231215
    • Accession Number:
      10.1046/j.1471-4159.2001.00013.x
    • Accession Number:
      11145991