Gene Symbol: Gnai1
Description: guanine nucleotide binding protein (G protein), alpha inhibiting 1
Alias: AU046200, Gialpha1, Gnai-1, guanine nucleotide-binding protein G(i) subunit alpha-1, adenylate cyclase-inhibiting G alpha protein, guanine nucleotide binding protein, alpha inhibiting 1
Species: mouse
Products:     Gnai1

Top Publications

  1. Jiang M, Spicher K, Boulay G, Martin Requero A, Dye C, Rudolph U, et al. Mouse gene knockout and knockin strategies in application to alpha subunits of Gi/Go family of G proteins. Methods Enzymol. 2002;344:277-98 pubmed
  2. Jones D, Reed R. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987;262:14241-9 pubmed
    ..In olfactory tissue, G alpha s was the most abundant of these messages and in combination with the biochemical studies suggests that G alpha s is the G-protein component of the olfactory signal transduction cascade. ..
  3. 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. ..
  4. Pratt C, Dionne L, Fairfield H, Dadras S, Potter C, Sundberg J. Gnaq(M1J): An ENU-Induced Mutant Allele Affecting Pigmentation in the Mouse. J Invest Dermatol. 2016;136:334-6 pubmed publisher
  5. Gaillard S, Lo Re L, Mantilleri A, Hepp R, Urien L, Malapert P, et al. GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia. Neuron. 2014;84:123-136 pubmed publisher
    ..These results further support the role of unmyelinated C fibers in injury-induced modulation of spinal GABAergic inhibition and identify GINIP as a key modulator of peripherally evoked GABAB-receptors signaling. ..
  6. Plummer N, Spicher K, Malphurs J, Akiyama H, Abramowitz J, Nurnberg B, et al. Development of the mammalian axial skeleton requires signaling through the G?(i) subfamily of heterotrimeric G proteins. Proc Natl Acad Sci U S A. 2012;109:21366-71 pubmed publisher
    ..Mice with mutations of Gnai1 or Gnai2 have neither defect, but loss of both Gnai3 and one of the other two genes increases the number and ..
  7. Young A, Jiang M, Wang Y, Ahmedli N, Ramirez J, Reese B, et al. Specific interaction of G?i3 with the Oa1 G-protein coupled receptor controls the size and density of melanosomes in retinal pigment epithelium. PLoS ONE. 2011;6:e24376 pubmed publisher
    ..Our results identify the Oa1 transducer G?i3 as the first downstream component in the Oa1 signaling pathway. ..
  8. Kim J, Kim Y, Ko J. CKbeta8/CCL23 and its isoform CKbeta8-1 induce up-regulation of cyclins via the G(i)/G(o) protein/PLC/PKCdelta/ERK leading to cell-cycle progression. Cytokine. 2010;50:42-9 pubmed publisher
    ..These results indicate that both CKbeta8 and CKbeta8-1 are involved in cell proliferation by modulating the cell cycle regulators. ..
  9. Tarchini B, Tadenev A, Devanney N, Cayouette M. A link between planar polarity and staircase-like bundle architecture in hair cells. Development. 2016;143:3926-3932 pubmed
    ..We propose that LGN and G?i participate in a long-inferred signal that originates outside the bundle to model its staircase-like architecture, a property that is essential for direction sensitivity to mechanical deflection and hearing. ..

More Information


  1. Simon K, Hennen S, Merten N, Blättermann S, Gillard M, Kostenis E, et al. The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules. J Biol Chem. 2016;291:705-18 pubmed publisher
    ..We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis. ..
  2. Vellano C, Brown N, Blumer J, Hepler J. Assembly and function of the regulator of G protein signaling 14 (RGS14)·H-Ras signaling complex in live cells are regulated by G?i1 and G?i-linked G protein-coupled receptors. J Biol Chem. 2013;288:3620-31 pubmed publisher
    ..Together, these findings indicate that inactive G?(i1)-GDP enhances the affinity of RGS14 for H-Ras-GTP in live cells, resulting in a ternary signaling complex that is further regulated by GPCRs. ..
  3. Tang G, Wang Y, Park S, Bajpayee N, Vi D, Nagaoka Y, et al. Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic ? cells. Proc Natl Acad Sci U S A. 2012;109:2636-41 pubmed publisher
    ..Our findings provide insight into galanin's action in glucose homeostasis. The results may also be relevant to the understanding of galanin signaling in other biological systems, especially the central nervous system. ..
  4. Ofek O, Attar Namdar M, Kram V, Dvir Ginzberg M, Mechoulam R, Zimmer A, et al. CB2 cannabinoid receptor targets mitogenic Gi protein-cyclin D1 axis in osteoblasts. J Bone Miner Res. 2011;26:308-16 pubmed publisher
    ..These data demonstrate that in osteoblasts CB2 targets a Gi protein-cyclin D1 mitogenic axis. Erk1/2 phosphorylation and Mapkapk2 protein synthesis are critical intermediates in this axis. ..
  5. Xiang B, Zhang G, Liu J, Morris A, Smyth S, Gartner T, et al. A G(i) -independent mechanism mediating Akt phosphorylation in platelets. J Thromb Haemost. 2010;8:2032-41 pubmed publisher
    ..Our results reveal a novel P2Y??-independent signaling pathway mediating Akt phosphorylation in response to thrombin receptors. ..
  6. Fleischer J, Schwarzenbacher K, Breer H. Expression of trace amine-associated receptors in the Grueneberg ganglion. Chem Senses. 2007;32:623-31 pubmed
  7. Nieswandt B, Schulte V, Zywietz A, Gratacap M, Offermanns S. Costimulation of Gi- and G12/G13-mediated signaling pathways induces integrin alpha IIbbeta 3 activation in platelets. J Biol Chem. 2002;277:39493-8 pubmed
  8. London B, Trudeau M, Newton K, Beyer A, Copeland N, Gilbert D, et al. Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current. Circ Res. 1997;81:870-8 pubmed
    ..This N-terminal Erg isoform may determine the properties of IKr and contribute to the pathogenesis of LQTS. ..
  9. Miao G, Smeyne R, D ARCANGELO G, Copeland N, Jenkins N, Morgan J, et al. Isolation of an allele of reeler by insertional mutagenesis. Proc Natl Acad Sci U S A. 1994;91:11050-4 pubmed
    ..Thus, unlike the two rl alleles described previously, rltg provides a molecular probe that can now be used to identify and isolate the rl gene. ..
  10. Sullivan K, Liao Y, Alborzi A, Beiderman B, Chang F, Masters S, et al. Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains. Proc Natl Acad Sci U S A. 1986;83:6687-91 pubmed
    ..Further comparison of the alpha-chain sequences suggests additional regions that may contribute to interactions with beta gamma subunits and the receptor and effector components of different signal transduction systems. ..
  11. Traver S, Bidot C, Spassky N, Baltauss T, de Tand M, Thomas J, et al. RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao. Biochem J. 2000;350 Pt 1:19-29 pubmed
  12. Wiege K, Le D, Syed S, Ali S, Novakovic A, Beer Hammer S, et al. Defective macrophage migration in G?i2- but not G?i3-deficient mice. J Immunol. 2012;189:980-7 pubmed publisher
    ..These results indicate that G?(i2), albeit redundant to G?(i3) in some macrophage activation processes, clearly exhibits a G?(i) isoform-specific role in the regulation of macrophage migration...
  13. Wang W, Schillinger R, Malone M, Liggett S. Paradoxical attenuation of ?2-AR function in airway smooth muscle by Gi-mediated counterregulation in transgenic mice overexpressing type 5 adenylyl cyclase. Am J Physiol Lung Cell Mol Physiol. 2011;300:L472-8 pubmed publisher
    ..ERK1/2 inhibition had no effect on the phenotype. Thus perturbing the ratio of ?(2)-AR to AC in ASM by increasing AC fails to improve (and actually decreases) ?-agonist efficacy due to counterregulatory events. ..
  14. Suzuki Y, Shen T, Poyard M, Best Belpomme M, Hanoune J, Defer N. Expression of adenylyl cyclase mRNAs in the denervated and in the developing mouse skeletal muscle. Am J Physiol. 1998;274:C1674-85 pubmed
    ..These results indicate that changes in AC activity and AC mRNAs play an important role in the various physiopathological states of skeletal muscle, especially during muscle atrophy. ..
  15. Zuberi Z, Birnbaumer L, Tinker A. The role of inhibitory heterotrimeric G proteins in the control of in vivo heart rate dynamics. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1822-30 pubmed publisher
    ..We have compared in vivo different groups of mice with global genetic deletion of Gialpha1/Galphai3, Galphai2, and Galphao against littermate controls using implanted ECG telemetry...
  16. Li X, Wang D, Chen Z, Lu E, Wang Z, Duan J, et al. G?i1 and G?i3 regulate macrophage polarization by forming a complex containing CD14 and Gab1. Proc Natl Acad Sci U S A. 2015;112:4731-6 pubmed publisher
    ..Collectively, the present findings demonstrated that G?i1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo. ..
  17. Huang W, Dai S, Chang Y, Sun W. Acidosis Mediates the Switching of Gs-PKA and Gi-PKCε Dependence in Prolonged Hyperalgesia Induced by Inflammation. PLoS ONE. 2015;10:e0125022 pubmed publisher
    ..Thus, acidosis in inflamed tissues may be a decisive factor to regulate switching of PKA and PKCε dependence via proton-sensing G-protein-coupled receptors. ..
  18. Rieken S, Herroeder S, Sassmann A, Wallenwein B, Moers A, Offermanns S, et al. Lysophospholipids control integrin-dependent adhesion in splenic B cells through G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11). J Biol Chem. 2006;281:36985-92 pubmed
    ..Taken together, this study shows that lysophospholipids regulate integrin-mediated adhesion of splenic B cells to ICAM-1 through G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11). ..
  19. Kask K, Ruisu K, Tikker L, Karis K, Saare M, Meier R, et al. Deletion of RIC8A in neural precursor cells leads to altered neurogenesis and neonatal lethality of mouse. Dev Neurobiol. 2015;75:984-1002 pubmed publisher
    ..Taken together, RIC8A has an essential role in the development of mammalian nervous system by maintaining the integrity of pial basement membrane and modulating cell division. ..
  20. Saare M, Lulla S, Tõnissoo T, Meier R, Kask K, Ruisu K, et al. Expression Pattern and Localization Dynamics of Guanine Nucleotide Exchange Factor RIC8 during Mouse Oogenesis. PLoS ONE. 2015;10:e0129131 pubmed publisher
    ..RIC8 is also expressed at high level in female reproductive organs e.g. oviduct. Therefore we suggest a regulatory function for RIC8 in mammalian gametogenesis and fertility. ..
  21. Villanueva H, Visbal A, Obeid N, Ta A, Faruki A, Wu M, et al. An essential role for Gα(i2) in Smoothened-stimulated epithelial cell proliferation in the mammary gland. Sci Signal. 2015;8:ra92 pubmed publisher
  22. Shen Y, Rampino M, Carroll R, Nawy S. G-protein-mediated inhibition of the Trp channel TRPM1 requires the G?? dimer. Proc Natl Acad Sci U S A. 2012;109:8752-7 pubmed publisher
    ..These results suggest a model in which the G?? dimer that is released as a result of the dissociation from G?(o) upon activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction. ..
  23. Fleischer J, Schwarzenbacher K, Besser S, Hass N, Breer H. Olfactory receptors and signalling elements in the Grueneberg ganglion. J Neurochem. 2006;98:543-54 pubmed
    ..Moreover, expression of a vomeronasal receptor indicates that the GG might serve to detect pheromones. ..
  24. Vellano C, Shu F, Ramineni S, Yates C, Tall G, Hepler J. Activation of the regulator of G protein signaling 14-G?i1-GDP signaling complex is regulated by resistance to inhibitors of cholinesterase-8A. Biochemistry. 2011;50:752-62 pubmed publisher
    ..These findings demonstrate that RGS14 is a newly appreciated integrator of unconventional Ric-8A and G?i1 signaling. ..
  25. Fan H, Zingarelli B, Peck O, Teti G, Tempel G, Halushka P, et al. Lipopolysaccharide- and gram-positive bacteria-induced cellular inflammatory responses: role of heterotrimeric Galpha(i) proteins. Am J Physiol Cell Physiol. 2005;289:C293-301 pubmed
    ..These data suggest that G(i) proteins differentially regulate murine TLR-mediated inflammatory cytokine production in a cell-specific manner in response to both LPS and gram-positive microbial stimuli. ..
  26. Kim S, Jin J, Kunapuli S. Akt activation in platelets depends on Gi signaling pathways. J Biol Chem. 2004;279:4186-95 pubmed
  27. Fan H, Williams D, Zingarelli B, Breuel K, Teti G, Tempel G, et al. Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in splenocytes by Galphai proteins. Biochim Biophys Acta. 2006;1763:1051-8 pubmed
  28. Fan H, Williams D, Zingarelli B, Breuel K, Teti G, Tempel G, et al. Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in macrophages by Galpha(i) proteins. Immunology. 2007;122:116-23 pubmed
    ..These data suggest that G(i2) and G(i1/3) proteins are both involved and differentially regulate murine inflammatory cytokine and chemokine production in response to both LPS and Gram-positive microbial stimuli. ..
  29. Cao C, Huang X, Han Y, Wan Y, Birnbaumer L, Feng G, et al. Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway. Sci Signal. 2009;2:ra17 pubmed publisher
    ..Overall, this study suggests that Galpha(i1) and Galpha(i3) lie downstream of EGFR, but upstream of Gab1-mediated activation of Akt and mTORC1, thus revealing a role for Galpha(i) proteins in mediating EGFR signaling. ..
  30. Blatt C, Eversole Cire P, Cohn V, Zollman S, Fournier R, Mohandas L, et al. Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human. Proc Natl Acad Sci U S A. 1988;85:7642-6 pubmed
    ..The retinal-specific transducin subunit genes GNAT1 and GNAT2 were on chromosomes 3 and 1; GNAI1, GNAI2, and GNAI3 were assigned to chromosomes 7, 3, and 1, respectively; GNAZ and GNAS were found on chromosomes ..
  31. Jiang M, Spicher K, Boulay G, Wang Y, Birnbaumer L. Most central nervous system D2 dopamine receptors are coupled to their effectors by Go. Proc Natl Acad Sci U S A. 2001;98:3577-82 pubmed
    ..In agreement with this, the effect of GTP on dopamine binding to D2 receptors in double Gi1 plus Gi2- and Gi1 plus Gi3-deficient mice was essentially unaffected. ..
  32. Lee C, Ahn H, Lee S, Shin J, Park W, Kim J, et al. Integrated analysis of omics data using microRNA-target mRNA network and PPI network reveals regulation of Gnai1 function in the spinal cord of Ews/Ewsr1 KO mice. BMC Med Genomics. 2016;9 Suppl 1:33 pubmed publisher
    ..On the biological side, we report that EWS regulates G-protein, Gnai1, in the spinal cord of Ews/Ewsr1 KO mice using the two biological network integrated analysis method...
  33. Lacomme M, Tarchini B, Boudreau Pinsonneault C, Monat C, Cayouette M. The LGN protein promotes planar proliferative divisions in the neocortex but apicobasal asymmetric terminal divisions in the retina. Development. 2016;143:575-81 pubmed publisher
  34. Marigo V, Roberts D, Lee S, Tsukurov O, Levi T, Gastier J, et al. Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. Genomics. 1995;28:44-51 pubmed
    ..Shh mapped to a position 0.6 cM distal to En2 and 1.9 cM proximal to Il6 on mouse chromosome 5. This location is closely linked but distinct from the murine limb mutation Hx and syntenic to human chromosome 7q36. ..
  35. Liu R, Ramani B, Soto D, De Arcangelis V, Xiang Y. Agonist dose-dependent phosphorylation by protein kinase A and G protein-coupled receptor kinase regulates beta2 adrenoceptor coupling to G(i) proteins in cardiomyocytes. J Biol Chem. 2009;284:32279-87 pubmed publisher
  36. DIEHL S, McElvany B, Noubade R, Seeberger N, Harding B, Spach K, et al. G proteins G?i1/3 are critical targets for Bordetella pertussis toxin-induced vasoactive amine sensitization. Infect Immun. 2014;82:773-82 pubmed publisher
    ..Finally, by using mice deficient in individual G?i/o G-protein subunits, we demonstrate that G?i1 and G?i3 are the critical in vivo targets of ADP-ribosylation underlying VAAS elicited by PTX exposure. ..
  37. Tarchini B, Jolicoeur C, Cayouette M. A molecular blueprint at the apical surface establishes planar asymmetry in cochlear hair cells. Dev Cell. 2013;27:88-102 pubmed publisher
    ..G?i is additionally required for lateral orientation of cochlear hair cells, providing a possible mechanism to couple the emergence of asymmetric stereocilia bundles with planar cell polarity. ..
  38. Yang X, Mei S, Wang X, Li X, Liu R, Ma Y, et al. Leucine facilitates insulin signaling through a G?i protein-dependent signaling pathway in hepatocytes. J Biol Chem. 2013;288:9313-20 pubmed publisher
    ..This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly. ..
  39. Lawler O, Miggin S, Kinsella B. Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to G(s)-, to G(i)-, and to G(q)-coupled effector signaling. J Biol Chem. 2001;276:33596-607 pubmed
  40. Wang Y, Park S, Bajpayee N, Nagaoka Y, Boulay G, Birnbaumer L, et al. Augmented glucose-induced insulin release in mice lacking G(o2), but not G(o1) or G(i) proteins. Proc Natl Acad Sci U S A. 2011;108:1693-8 pubmed publisher
    ..We thus provide unique genetic evidence that the G(o2) protein is a transducer in an inhibitory pathway that prevents damaging oversecretion of insulin. ..
  41. Orth J, Fester I, Preuss I, Agnoletto L, Wilson B, Aktories K. Activation of Galpha (i) and subsequent uncoupling of receptor-Galpha(i) signaling by Pasteurella multocida toxin. J Biol Chem. 2008;283:23288-94 pubmed publisher
    ..The data indicate that PMT is a novel activator of G(i), modulating its GTPase activity and converting it into a PTx-insensitive state...
  42. Pineda V, Athos J, Wang H, Celver J, Ippolito D, Boulay G, et al. Removal of G(ialpha1) constraints on adenylyl cyclase in the hippocampus enhances LTP and impairs memory formation. Neuron. 2004;41:153-63 pubmed
    ..We hypothesize that loss of G(ialpha1) amplifies the responsiveness of CA1 postsynaptic neurons to stimuli that strengthen synaptic efficacy, thereby diminishing synapse-specific plasticity required for new memory formation. ..
  43. Vellano C, Maher E, Hepler J, Blumer J. G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·G?i1 complex in live cells. J Biol Chem. 2011;286:38659-69 pubmed publisher
    ..Together, these findings indicate that RGS14 can form complexes with GPCRs in cells that are dependent on G?(i/o) and that these RGS14·G?(i1)·GPCR complexes may be substrates for other signaling partners such as Ric-8A. ..