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Gnao1  -  guanine nucleotide binding protein, alpha O

Mus musculus

Synonyms: AW050213, Galphao, Gna0, Gnao, Go alpha, ...
 
 
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Disease relevance of Gnao1

  • By screening of a cDNA library from rat C6 glioma cells with a synthetic probe corresponding to a 17 amino acid sequence, a clone encoding the sequence of Go alpha was obtained [1].
  • The RAW264 pertussis toxin substrate was not recognized by either antibody CW/6 or antibody RV/3, which recognize the 41-kilodalton alpha-subunit of brain Gi (Gi-1-alpha) and Go-alpha, respectively [2].
  • To determine unambiguously whether the two Go alpha subunits detected in neuroblastoma cells were actually the products of different mRNAs, rabbit polyclonal antibodies were generated against synthetic peptides (amino acids 291-302) of both sequences [3].
  • In purified G proteins from bovine brain cortex the ADP-ribosylated substrates of Bordetella pertussis toxin (PT) can be resolved in three polypeptides by polyacrylamide gel electrophoresis: a 39 kDa major substrate, corresponding to Go alpha and two others (40 and 41 kDa) assigned to alpha subunits of Gi-like proteins [4].
 

High impact information on Gnao1

  • The alpha subunit of the guanine nucleotide-binding protein Go ("o" for other) is believed to mediate signal transduction between a variety of receptors and effectors. cDNA clones encoding two forms of Go alpha subunit were isolated from a mouse brain library [5].
  • The Go alpha clone encoded a sequence of 310 amino acid residues that lacked the NH2 terminus [1].
  • Different forms of Go alpha mRNA arise by alternative splicing of transcripts from a single gene on human chromosome 16 [6].
  • ADP-ribosylation with 32P-NAD and PTX of choroid plexus revealed an intense labeling at the 40 kDa level in addition to the known PTX-substrates at 41 kDa (Gi alpha) and 39 kDa (Go alpha) [7].
  • However, a positive immunoreactivity with the anti-Go alpha antibodies was detected at the level of the 39 kDa faster component, indicating the presence of Go alpha in both choroid plexuses and cultured ependymal cells [7].
 

Biological context of Gnao1

  • Purified preparations of Gi and Go alpha subunits (Gi alpha and Go alpha) from rat brain were completely digested with trypsin, and peptides were subjected to amino acid sequence analysis [1].
  • One, MAB1, cross-reacted strongly with the alpha-subunit of Gi (Gi alpha) purified from rabbit liver and, to a lesser extent, with the alpha-subunit of Go (Go alpha) purified from bovine brain and the proto-oncogene product H-ras p21 [8].
  • We conclude that Go alpha mRNAs with different 3' UTRs arise by alternative splicing of transcripts from a single gene [6].
  • It can be concluded that the degradation rate of the more basic Go alpha isoform is not a characteristic of the protein itself but depends on the state of the cell differentiation [9].
  • Study of the ontogenesis of both Go alpha subunits revealed the predominance of Go2 alpha in the frontal cortex at day 15 of gestation [3].
 

Anatomical context of Gnao1

  • Immunoblotting experiments with selective affinity-purified polyclonal rabbit antibodies to the 39 kDa alpha subunit of Go (Go alpha) indicated that Go is distributed in both neurons and glial cells [10].
  • At the ultrastructural level, using gold immunoprobes, the immunoreactivity of a Go alpha-like protein was detected on the cytoplasmic face of the apical plasma membrane, coated pits and vesicles, and in the apical cytoplasmic matrix [7].
  • In thin frozen sections as well as in cultured cells, Go alpha was mainly immunolocalized at the apical pole of choroidal ependymocytes and in the kinocilia of ciliated ependymal cells [7].
  • Indirect immunofluorescence staining of cerebellar granule cells and striatal neurons with purified Go alpha antibodies was pronounced at the plasma membrane level, particularly at cell-cell contact areas, and in neurite arborization [10].
  • The steady-state level Go alpha, a major substrate for pertussis toxin-catalyzed ADP-ribosylation, was unaltered by pertussis toxin treatment for periods up to 100 h for 3T3-L1 cells in culture or up to 3 days in vivo [11].
 

Associations of Gnao1 with chemical compounds

  • On a blotted mixture of purified brain guanine nucleotide-binding proteins, the anti-alpha o1 and anti-alpha o2 peptide antibodies only recognized the 39-kDa Go alpha subunit [3].
  • Myr+-Gi2 alpha and Go alpha subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice [12].
  • Mastoparan after binding to Gi alpha/Go alpha subunits could block opioid antinociception [13].
  • Treatment of cells with 0.1 microM 8-bromoadenosine 3',5'-(cyclic)phosphate (BrcAMP) for 16 h, or with 0.1 mM BrcAMP for 5 min, mimicked the effect of cholera toxin on the ADP-ribosylation of Go alpha and Gi alpha in vitro [14].
  • Serial sections showed that Go alpha-positive cells were immunostained for calcitonin gene-related peptide and serotonin in young adult mouse, rat, and hamster lungs and that these cells are, therefore, PNECs [15].
 

Other interactions of Gnao1

  • However, Go alpha, but not Gs alpha or Gi alpha, reacted strongly with the antibodies when the native subunit was spotted directly [16].
  • Proteolytic experiments performed on transducin and Go alpha subunit strongly suggest that the amino-terminal residues of the alpha chain are involved in the interaction with beta gamma subunits [17].
  • 32P-ADP-ribosylation of the same neuronal and glial cell membranes with pertussis toxin indicated the presence of at least 3 substrates related to Go alpha, Gi alpha (41 kDa), and a 40 kDa protein [10].
  • Immunoblots detected the presence of the G-proteins Gi alpha 2, Gi alpha 3, and Go alpha 2 [18].
  • The t 1/2 for total Go alpha protein degradation was very different in the three neuronal cell populations and was 28 +/- 5 h (n = 5), 58 +/- 9 h (n = 5), and 154 +/- 22 h (n = 6) in undifferentiated, differentiated neuroblastoma, and granule cells, respectively [9].
 

Analytical, diagnostic and therapeutic context of Gnao1

  • Northern blotting indicated that among the IAP-sensitive G-proteins, the levels of Gi2 alpha, Go alpha, and Gi3 alpha mRNA were decreased, increased and unchanged, respectively [19].

References

  1. Molecular cloning and sequence determination of cDNAs for alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. Itoh, H., Kozasa, T., Nagata, S., Nakamura, S., Katada, T., Ui, M., Iwai, S., Ohtsuka, E., Kawasaki, H., Suzuki, K. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  2. Immunochemical and electrophoretic characterization of the major pertussis toxin substrate of the RAW264 macrophage cell line. Backlund, P.S., Aksamit, R.R., Unson, C.G., Goldsmith, P., Spiegel, A.M., Milligan, G. Biochemistry (1988) [Pubmed]
  3. Specific antibodies against Go isoforms reveal the early expression of the Go2 alpha subunit and appearance of Go1 alpha during neuronal differentiation. Rouot, B., Charpentier, N., Chabbert, C., Carrette, J., Zumbihl, R., Bockaert, J., Homburger, V. Mol. Pharmacol. (1992) [Pubmed]
  4. Multiple species and isoforms of Bordetella pertussis toxin substrates. Brabet, P., Pantaloni, C., Rouot, B., Toutant, M., Garcia-Sainz, A., Bockaert, J., Homburger, V. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  5. Alternative splicing produces transcripts encoding two forms of the alpha subunit of GTP-binding protein Go. Strathmann, M., Wilkie, T.M., Simon, M.I. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  6. Different forms of Go alpha mRNA arise by alternative splicing of transcripts from a single gene on human chromosome 16. Murtagh, J.J., Eddy, R., Shows, T.B., Moss, J., Vaughan, M. Mol. Cell. Biol. (1991) [Pubmed]
  7. Apical localization of the alpha subunit of GTP-binding protein Go in choroidal and ciliated ependymocytes. Péraldi, S., Nguyen Than Dao, B., Brabet, P., Homburger, V., Rouot, B., Toutant, M., Bouille, C., Assenmacher, I., Bockaert, J., Gabrion, J. J. Neurosci. (1989) [Pubmed]
  8. Structural and functional characterization of guanyl nucleotide-binding proteins using monoclonal antibodies to the alpha-subunit of transducin. Halpern, J.L., Tsai, S.C., Adamik, R., Kanaho, Y., Bekesi, E., Kung, H.F., Moss, J., Vaughan, M. Mol. Pharmacol. (1986) [Pubmed]
  9. Metabolism of two Go alpha isoforms in neuronal cells during differentiation. Brabet, P., Pantaloni, C., Bockaert, J., Homburger, V. J. Biol. Chem. (1991) [Pubmed]
  10. Immunocytochemical localization of the guanine nucleotide-binding protein Go in primary cultures of neuronal and glial cells. Brabet, P., Dumuis, A., Sebben, M., Pantaloni, C., Bockaert, J., Homburger, V. J. Neurosci. (1988) [Pubmed]
  11. Pertussis toxin treatment in vivo is associated with a decline in G-protein beta-subunits. Watkins, D.C., Northup, J.K., Malbon, C.C. J. Biol. Chem. (1989) [Pubmed]
  12. Myr+-Gi2 alpha and Go alpha subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice. Garzón, J., Rodríguez-Díaz, M., DeAntonio, I., DeFelipe, J., Rodríguez, J.R., Sánchez-Blázquez, P. Neuropharmacology (1999) [Pubmed]
  13. Mastoparan reduces the supraspinal analgesia mediated by mu/delta-opioid receptors in mice. Sánchez-Blázquez, P., Garzón, J. Eur. J. Pharmacol. (1994) [Pubmed]
  14. Treatment of intact striatal neurones with cholera toxin or 8-bromoadenosine 3',5'-(cyclic)phosphate decreases the ability of pertussis toxin to ADP-ribosylate the alpha-subunits of inhibitory and other guanine-nucleotide-binding regulatory proteins, Gi and Go. Evidence for two distinct mechanisms. Maus, M., Homburger, V., Cordier, J., Pantaloni, C., Bockaert, J., Glowinski, J., Prémont, J. Eur. J. Biochem. (1991) [Pubmed]
  15. Ontogeny of pulmonary neuroendocrine cells which express the alpha-subunit of guanine nucleotide-binding protein Go. Ito, T., Udaka, N., Kawano, N., Nogawa, H., Kitamura, H. Histochem. Cell Biol. (1999) [Pubmed]
  16. Relationships within the family of GTP-binding proteins isolated from bovine central nervous system. Roof, D.J., Applebury, M.L., Sternweis, P.C. J. Biol. Chem. (1985) [Pubmed]
  17. Deletion within the amino-terminal region of Gs alpha impairs its ability to interact with beta gamma subunits and to activate adenylate cyclase. Journot, L., Pantaloni, C., Bockaert, J., Audigier, Y. J. Biol. Chem. (1991) [Pubmed]
  18. Morphological and functional characterization of beta TC-6 cells--an insulin-secreting cell line derived from transgenic mice. Poitout, V., Stout, L.E., Armstrong, M.B., Walseth, T.F., Sorenson, R.L., Robertson, R.P. Diabetes (1995) [Pubmed]
  19. Possible involvement of phosphatidylinositol-specific phospholipase C related to pertussis toxin-sensitive GTP-binding proteins during adipocyte differentiation of 3T3-L1 fibroblasts: negative regulation of protein kinase C. Uehara, T., Hoshino, S., Ui, M., Tokumitsu, Y., Nomura, Y. Biochim. Biophys. Acta (1994) [Pubmed]
 
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