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Gnai2  -  guanine nucleotide binding protein (G...

Mus musculus

Synonyms: Adenylate cyclase-inhibiting G alpha protein, C76432, Galphai2, Gia, Gnai-2, ...
 
 
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Disease relevance of Gnai2

  • METHODS: A total of 284 F2 mice derived from resistant C57BL/6J Gnai2 -/- mice and susceptible C3H/HeN Gnai2 -/- mice were analyzed in a genome-wide screen for colitis susceptibility and severity [1].
  • BACKGROUND & AIMS: Mice with a disrupted gene for the G-protein alpha inhibitory 2 chain ( Gnai2 -/- ) develop a spontaneous colitis resembling human inflammatory bowel disease [1].
  • Short- and long-term regulation of adenylyl cyclase activity by delta-opioid receptor are mediated by Galphai2 in neuroblastoma N2A cells [2].
  • The reactivity of Peyer's patch (PP) and lamina propria (LP) T and B lymphocytes in inhibitory G-protein alpha2 subunit-deficient (Galphai2-/-) mice developing an IBD resembling ulcerative colitis was investigated following repeated oral immunizations with keyhole limpet haemocyanin (KLH), together with the adjuvant cholera toxin, prior to colitis [3].
  • In vitro stimulation of splenocytes with formalin-killed Staphylococcus aureus resulted in significantly increased production of interleukin-1beta, tumor necrosis factor, and interleukin-12p40 in Galphai2(-/-) as compared to control mice [4].
 

High impact information on Gnai2

  • These results demonstrate opposing roles for Rgs1 and Gnai2 in B cell trafficking into and within lymph nodes [5].
  • In contrast, B cells from Gnai2-/- mice enter lymph nodes poorly and move more slowly than do wild-type B cells [5].
  • No changes in betaAR number, or in the heterotrimeric GTP-binding proteins, Galphas or Galphai2, were observed [6].
  • Pleiotropic phenotype of a genomic knock-in of an RGS-insensitive G184S Gnai2 allele [7].
  • To unambiguously identify the pertussis toxin (PTX)-sensitive G-proteins responsible for inhibition and sensitization, we used viral-mediated gene delivery to assess the ability of genetically engineered PTX-resistant G-proteins (Galphai1*, Galphai2*, Galphai3*, and Galphao*) to rescue both responses after PTX treatment [8].
 

Chemical compound and disease context of Gnai2

 

Biological context of Gnai2

 

Anatomical context of Gnai2

  • The Gnai2-/- mice often lack multiple peripheral lymph nodes, and their B cells respond poorly to chemokines, indicating that Galpha(i1) and Galpha(i3) poorly compensate for the loss of Galpha(i2) [5].
  • Oocytes coexpressing GB1aR + Galphai2-fused GB2R (GB2R-Galphai2) caused faster K+ currents in response to baclofen [14].
  • Galphai2-/- mice are deficient in the formation of certain B and T cell subsets and are susceptible to immune dysregulation, notably developing inflammatory bowel disease [15].
  • Analysis of T cell responses following restimulation ex vivo with KLH revealed a dramatic increase in the production of interferon-gamma in mesenteric lymph node, PP and LP lymphocytes from Galphai2-deficient as compared to wild-type mice, together with decreased production of interleukin-10 in all locations except the PP [3].
  • Glycogen synthase in skeletal muscle was found to be activated in Q205L Galphai2-expressing mice, in the absence of the administration of insulin [12].
 

Associations of Gnai2 with chemical compounds

  • Distinct roles for Galphai2, Galphai3, and Gbeta gamma in modulation offorskolin- or Gs-mediated cAMP accumulation and calcium mobilization by dopamine D2S receptors [16].
  • We found that RGS14 inhibits guanine nucleotide exchange on Galphai1 and Galphai3 could, but not Galphai2 [17].
  • Cytokine hyper-responsiveness was not seen when purified Galphai2(-/-) T cells were stimulated with phorbol myristic acetate/ionomycin, localizing the alteration to a proximal TCR-specific signaling pathway [18].
 

Regulatory relationships of Gnai2

  • In vitro, the B cell population of Galphai2(-/-) mice was functionally deficient in LPS-induced proliferation and IL-10 production, consistent with the exclusive capacity of T2 and MZ cell subpopulations for LPS responsiveness [10].
 

Other interactions of Gnai2

  • In this study, we addressed the hypothesis that Galphai2 is required for the development of IL-10-producing B cells [10].
  • Reconstitution of RAG2(-/-) mice with Galphai2(-/-) bone marrow induced an IBD-like colitis and a deficiency in absolute numbers of MZ, T2, and B-1 B cells [10].
  • The mRNAs encoding subunits Galphaq, Galphao, Galphai-2, and Galphaz are expressed in the cerebellar anlage at least from embryonic day 14 onward, and relative levels of these mRNAs do not change appreciably from E14 to adulthood [19].
  • Of the known Ptx-sensitive G-protein alpha subunits, MN9D-expressed Galphai2, GalphaoA, and GalphaoB; however, none of these coupled to the D4 receptor [20].
  • Enhanced pro-inflammatory cytokine production in Galphai2-deficient mice on colitis prone and colitis resistant 129Sv genetic backgrounds [4].
 

Analytical, diagnostic and therapeutic context of Gnai2

References

  1. A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models. Borm, M.E., He, J., Kelsall, B., Peña, A.S., Strober, W., Bouma, G. Gastroenterology (2005) [Pubmed]
  2. Short- and long-term regulation of adenylyl cyclase activity by delta-opioid receptor are mediated by Galphai2 in neuroblastoma N2A cells. Zhang, L., Tetrault, J., Wang, W., Loh, H.H., Law, P.Y. Mol. Pharmacol. (2006) [Pubmed]
  3. Impaired B cell responses to orally administered antigens in lamina propria but not Peyer's patches of Galphai2-deficient mice prior to colitis. Ohman, L., Aström, R.G., Hultgren Hörnquist, E. Immunology (2005) [Pubmed]
  4. Enhanced pro-inflammatory cytokine production in Galphai2-deficient mice on colitis prone and colitis resistant 129Sv genetic backgrounds. Bjursten, M., Hultgren, O.H., Hultgren Hörnquist, E. Cell. Immunol. (2004) [Pubmed]
  5. Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. Han, S.B., Moratz, C., Huang, N.N., Kelsall, B., Cho, H., Shi, C.S., Schwartz, O., Kehrl, J.H. Immunity (2005) [Pubmed]
  6. Increased expression of adenylylcyclase type VI proportionately increases beta-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes. Gao, M., Ping, P., Post, S., Insel, P.A., Tang, R., Hammond, H.K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Pleiotropic phenotype of a genomic knock-in of an RGS-insensitive G184S Gnai2 allele. Huang, X., Fu, Y., Charbeneau, R.A., Saunders, T.L., Taylor, D.K., Hankenson, K.D., Russell, M.W., D'Alecy, L.G., Neubig, R.R. Mol. Cell. Biol. (2006) [Pubmed]
  8. Selective activation of Galphao by D2L dopamine receptors in NS20Y neuroblastoma cells. Watts, V.J., Wiens, B.L., Cumbay, M.G., Vu, M.N., Neve, R.L., Neve, K.A. J. Neurosci. (1998) [Pubmed]
  9. Long-term treatment with anti-alpha 4 integrin antibodies aggravates colitis in G alpha i2-deficient mice. Bjursten, M., Bland, P.W., Willén, R., Hörnquist, E.H. Eur. J. Immunol. (2005) [Pubmed]
  10. B cell developmental requirement for the G alpha i2 gene. Dalwadi, H., Wei, B., Schrage, M., Spicher, K., Su, T.T., Birnbaumer, L., Rawlings, D.J., Braun, J. J. Immunol. (2003) [Pubmed]
  11. Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets. Wei, B., Velazquez, P., Turovskaya, O., Spricher, K., Aranda, R., Kronenberg, M., Birnbaumer, L., Braun, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Conditional, tissue-specific expression of Q205L Galphai2 in vivo mimics insulin activation of c-Jun N-terminal kinase and p38 kinase. Guo, J.H., Wang, H.Y., Malbon, C.C. J. Biol. Chem. (1998) [Pubmed]
  13. Signaling through G{alpha}i2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice. Padigel, U.M., Stein, L., Redding, K., Lee, J.J., Nolan, T.J., Schad, G.A., Birnbaumer, L., Abraham, D. J. Leukoc. Biol. (2007) [Pubmed]
  14. Coupling of GABAB receptor GABAB2 subunit to G proteins: evidence from Xenopus oocyte and baby hamster kidney cell expression system. Uezono, Y., Kanaide, M., Kaibara, M., Barzilai, R., Dascal, N., Sumikawa, K., Taniyama, K. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  15. Formation of B and T cell subsets require the cannabinoid receptor CB2. Ziring, D., Wei, B., Velazquez, P., Schrage, M., Buckley, N.E., Braun, J. Immunogenetics (2006) [Pubmed]
  16. Distinct roles for Galphai2, Galphai3, and Gbeta gamma in modulation offorskolin- or Gs-mediated cAMP accumulation and calcium mobilization by dopamine D2S receptors. Ghahremani, M.H., Cheng, P., Lembo, P.M., Albert, P.R. J. Biol. Chem. (1999) [Pubmed]
  17. The RGS14 GoLoco domain discriminates among Galphai isoforms. Mittal, V., Linder, M.E. J. Biol. Chem. (2004) [Pubmed]
  18. TCR-mediated hyper-responsiveness of autoimmune Galphai2(-/-) mice is an intrinsic naïve CD4(+) T cell disorder selective for the Galphai2 subunit. Huang, T.T., Zong, Y., Dalwadi, H., Chung, C., Miceli, M.C., Spicher, K., Birnbaumer, L., Braun, J., Aranda, R. Int. Immunol. (2003) [Pubmed]
  19. Developmental expression of heterotrimeric G-proteins in the murine cerebellar cortex. Schüller, U., Lamp, E.C., Schilling, K. Histochem. Cell Biol. (2001) [Pubmed]
  20. The rat D4 dopamine receptor couples to cone transducin (Galphat2) to inhibit forskolin-stimulated cAMP accumulation. Yamaguchi, I., Harmon, S.K., Todd, R.D., O'Malley, K.L. J. Biol. Chem. (1997) [Pubmed]
  21. RGS-Rz and RGS9-2 proteins control mu-opioid receptor desensitisation in CNS: the role of activated Galphaz subunits. Sánchez-Blázquez, P., Rodríguez-Muñoz, M., Montero, C., Garzón, J. Neuropharmacology (2005) [Pubmed]
  22. Transfer of colitis by Galphai2-deficient T lymphocytes: impact of subpopulations and tissue origin. Bjursten, M., Willén, R., Hultgren Hörnquist, E. Inflamm. Bowel Dis. (2005) [Pubmed]
  23. Modulation of adenylyl cyclase by FPP and adenosine involves stimulatory and inhibitory adenosine receptors and g proteins. Fraser, L.R., Adeoya-Osiguwa, S. Mol. Reprod. Dev. (1999) [Pubmed]
 
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