Gene Symbol: Gnaz
Description: guanine nucleotide binding protein, alpha z subunit
Alias: AI847979, guanine nucleotide-binding protein G(z) subunit alpha, g(x) alpha chain, gz-alpha
Species: mouse
Products:     Gnaz

Top Publications

  1. Schuller U, Lamp E, Schilling K. Developmental expression of heterotrimeric G-proteins in the murine cerebellar cortex. Histochem Cell Biol. 2001;116:149-59 pubmed
  2. Woulfe D, Jiang H, Mortensen R, Yang J, Brass L. Activation of Rap1B by G(i) family members in platelets. J Biol Chem. 2002;277:23382-90 pubmed
    ..In summary, activation of Rap1 can be stimulated by G(alpha)(i)- and PI3K-dependent mechanisms in platelets and by G(q)- and Ca(2+)-dependent mechanisms, both of which may play a role in promoting platelet activation. ..
  3. Yang J, Wu J, Kowalska M, Dalvi A, Prevost N, O Brien P, et al. Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs. Proc Natl Acad Sci U S A. 2000;97:9984-9 pubmed
    ..Therefore, these results provide insights into receptor selectivity among G proteins and a model for understanding platelet function and the effects of psychoactive drugs. ..
  4. Yang J, Wu J, Jiang H, Mortensen R, Austin S, Manning D, et al. Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem. 2002;277:46035-42 pubmed
    ..Finally, the failure of ADP and epinephrine to inhibit basal, as opposed to PGI(2)-stimulated, cAMP formation highlights the need during platelet activation for G(i) signaling pathways that involve effectors other than adenylyl cyclase. ..
  5. Jin S, Martinelli D, Zheng X, Tessier Lavigne M, Fan C. Gas1 is a receptor for sonic hedgehog to repel enteric axons. Proc Natl Acad Sci U S A. 2015;112:E73-80 pubmed publisher
    ..Of the Gαi proteins that can couple with Smo, G protein α Z (Gnaz) is found in enteric axons...
  6. Kelleher K, Matthaei K, Leck K, Hendry I. Developmental expression of messenger RNA levels of the alpha subunit of the GTP-binding protein, Gz, in the mouse nervous system. Brain Res Dev Brain Res. 1998;107:247-53 pubmed
    ..This further strengthens the hypothesis that Gzalpha is important in the transfer of information from target tissues to the innervating nerve cells. ..
  7. Camerer E, Barker A, Duong D, Ganesan R, Kataoka H, Cornelissen I, et al. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010;18:25-38 pubmed publisher
    ..Together, our results suggest a role for protease-activated receptor signaling in neural tube closure and identify a local protease network that may trigger Par2 signaling and monitor and regulate epithelial integrity in this context. ..
  8. Sánchez Blázquez P, Rodríguez Muñoz M, de la Torre Madrid E, Garzón J. Brain-specific Galphaz interacts with Src tyrosine kinase to regulate Mu-opioid receptor-NMDAR signaling pathway. Cell Signal. 2009;21:1444-54 pubmed publisher
    ..Most relevant, this mechanism which operates in neural cells is essential for the development of tolerance to the analgesic effects of morphine. ..
  9. Hendry I, Kelleher K, Bartlett S, Leck K, Reynolds A, Heydon K, et al. Hypertolerance to morphine in G(z alpha)-deficient mice. Brain Res. 2000;870:10-9 pubmed
    ..Our results suggest that the presence of G(z alpha) delays the development of morphine tolerance and represents a possible therapeutic target for improving the clinical use of morphine. ..

More Information


  1. Garzón J, de la Torre Madrid E, Rodríguez Muñoz M, Vicente Sánchez A, Sánchez Blázquez P. Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine. Mol Pain. 2009;5:11 pubmed publisher
    ..These Gz proteins are also responsible for the long-term analgesic tolerance produced by single doses of these agonists, as well as for the cross-tolerance between CB1Rs and MORs. ..
  2. Nagahama M, Usui S, Shinohara T, Yamaguchi T, Tani K, Tagaya M. Inactivation of Galpha(z) causes disassembly of the Golgi apparatus. J Cell Sci. 2002;115:4483-93 pubmed
    ..These results taken together suggest a general regulatory role for Galpha(z) in the control of the Golgi structure. ..
  3. Vancura P, Abdelhadi S, Csicsely E, Baba K, Tosini G, Iuvone P, et al. Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors. PLoS ONE. 2017;12:e0187411 pubmed publisher
    ..The gene Gnaz-a unique Gi/o subfamily member-was seen in the present study to be expressed in photoreceptors where its protein ..
  4. Mei H, Ho M, Yung L, Wu Z, Ip N, Wong Y. Expression of G?(z) in C2C12 cells restrains myogenic differentiation. Cell Signal. 2011;23:389-97 pubmed publisher
    ..These results support a novel role of G?(z) in restraining myogenic differentiation through the disruption of Rho signaling. ..
  5. Kimple M, Joseph J, Bailey C, Fueger P, Hendry I, Newgard C, et al. Galphaz negatively regulates insulin secretion and glucose clearance. J Biol Chem. 2008;283:4560-7 pubmed
    ..These findings indicate that Galphaz may be a potential new target for therapeutics aimed at ameliorating beta-cell dysfunction in Type 2 diabetes. ..
  6. Oleskevich S, Leck K, Matthaei K, Hendry I. Enhanced serotonin response in the hippocampus of Galphaz protein knock-out mice. Neuroreport. 2005;16:921-5 pubmed
    ..These results suggest that the 5HT1A receptor may be linked to Galphaz protein, as reported previously in cell culture but shown here in an intact neural network. ..
  7. Strathmann M, Wilkie T, Simon M. Diversity of the G-protein family: sequences from five additional alpha subunits in the mouse. Proc Natl Acad Sci U S A. 1989;86:7407-9 pubmed
    ..In addition, we found sequences corresponding to five newly discovered alpha subunits. Our results suggest that the complexity of the G protein family is much greater than previously suspected. ..
  8. Meng J, Casey P. Activation of Gz attenuates Rap1-mediated differentiation of PC12 cells. J Biol Chem. 2002;277:43417-24 pubmed
    ..The implications of these findings in regard to a possible role for G(z) in neuronal development are discussed. ..
  9. Chen L, Gilman A, Kozasa T. A candidate target for G protein action in brain. J Biol Chem. 1999;274:26931-8 pubmed
    ..Coexpression of GRIN1 or GRIN2 with activated G(o)alpha causes formation of a network of fine processes in Neuro2a cells, suggesting that these pathways may function downstream of G(o)alpha to control growth of neurites. ..
  10. Zobeley E, Sufalko D, Adkins S, Burmeister M. Fine genetic and comparative mapping of the deafness mutation Ames waltzer on mouse chromosome 10. Genomics. 1998;50:260-6 pubmed
    ..In addition, nine different genes (Ank3, Bcr, Gnaz, Tfam, Mif, Mmp11, Dcoh, Pyp, and Gstt2) were mapped and eliminated genetically as candidate genes for av...
  11. Tanabe T, Nukada T, Nishikawa Y, Sugimoto K, Suzuki H, Takahashi H, et al. Primary structure of the alpha-subunit of transducin and its relationship to ras proteins. Nature. 1985;315:242-5 pubmed
    ..The homologous segments correspond mostly to the regions thought to be involved in the guanine nucleotide binding and GTPase activity of ras proteins and to the ADP-ribosylation sites of the transducin alpha-subunit. ..
  12. Leck K, Bartlett S, Smith M, Megirian D, Holgate J, Powell K, et al. Deletion of guanine nucleotide binding protein alpha z subunit in mice induces a gene dose dependent tolerance to morphine. Neuropharmacology. 2004;46:836-46 pubmed
    ..The results suggest that G(z) signaling pathways are involved in transducing the analgesic and lethality effects of morphine following chronic morphine treatment. ..
  13. van den Buuse M, Martin S, Holgate J, Matthaei K, Hendry I. Mice deficient in the alpha subunit of G(z) show changes in pre-pulse inhibition, anxiety and responses to 5-HT(1A) receptor stimulation, which are strongly dependent on the genetic background. Psychopharmacology (Berl). 2007;195:273-83 pubmed
    ..Therefore, our results suggest caution when studying the behavioural effects of genetic modifications only in C57Bl/6 mice. ..
  14. Powell K, Matthaei K, Heydon K, Hendry I. G(z alpha) deficient mice: enzyme levels in the autonomic nervous system, neuronal survival and effect of genetic background. Int J Dev Neurosci. 2002;20:39-46 pubmed
    ..This suggests that in vivo other pertussis toxin sensitive G proteins may be recruited to compensate for the loss of G(z alpha). ..
  15. Kelleher K, Matthaei K, Hendry I. Targeted disruption of the mouse Gz-alpha gene: a role for Gz in platelet function?. Thromb Haemost. 2001;85:529-32 pubmed
    ..Ignoring the genetic background of a mutant mouse might lead to a misinterpretation of results and thus it is absolutely critical to take the genetic background into account when assessing any aspect of a mutant mouse. ..
  16. Kimple M, Moss J, Brar H, Rosa T, Truchan N, Pasker R, et al. Deletion of G?Z protein protects against diet-induced glucose intolerance via expansion of ?-cell mass. J Biol Chem. 2012;287:20344-55 pubmed publisher
    ..These results, along with those of our previous work, link signaling through G?(z) to both major aspects of ?-cell decompensation: insufficient ?-cell function and mass. ..
  17. Regard J, Malhotra D, Gvozdenovic Jeremic J, Josey M, Chen M, Weinstein L, et al. Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med. 2013;19:1505-12 pubmed publisher
  18. van den Buuse M, Martin S, Brosda J, Leck K, Matthaei K, Hendry I. Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of G(z). Psychopharmacology (Berl). 2005;183:358-67 pubmed
    ..These results suggest a possible role for G(z) in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia. ..
  19. Zigman J, Westermark G, LaMendola J, Steiner D. Expression of cone transducin, Gz alpha, and other G-protein alpha-subunit messenger ribonucleic acids in pancreatic islets. Endocrinology. 1994;135:31-7 pubmed
    ..cells express at least seven G alpha-subunits: G8 alpha, Gi1 alpha or Gi3 alpha, Gi2 alpha, G11 alpha, G14 alpha, Gz alpha, and Gt2 alpha (cone transducin)...
  20. Fenske R, Cadena M, Harenda Q, Wienkes H, Carbajal K, Schaid M, et al. The Inhibitory G Protein ?-Subunit, G?z, Promotes Type 1 Diabetes-Like Pathophysiology in NOD Mice. Endocrinology. 2017;158:1645-1658 pubmed publisher
  21. Fong H, Yoshimoto K, Eversole Cire P, Simon M. Identification of a GTP-binding protein alpha subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Proc Natl Acad Sci U S A. 1988;85:3066-70 pubmed
    ..and signal transduction in the retina, we have identified a G-protein alpha subunit, which we refer to as Gz alpha, by isolating a human retinal cDNA clone that cross-hybridizes at reduced stringency with bovine Tr alpha-subunit ..