Genomes and Genes
Gene Symbol: Gnai3
Description: guanine nucleotide binding protein (G protein), alpha inhibiting 3
Alias: AI158965, AW537698, Galphai3, Gnai-3, guanine nucleotide-binding protein G(k) subunit alpha, g(i) alpha-3, guanine nucleotide binding protein, alpha inhibiting 3
- Nagata K, Ye C, Jain M, Milstone D, Liao R, Mortensen R. Galpha(i2) but not Galpha(i3) is required for muscarinic inhibition of contractility and calcium currents in adult cardiomyocytes. Circ Res. 2000;87:903-9 pubmed..This study demonstrates that Galpha(i2), but not Galpha(i3), is required for muscarinic inhibition of the beta-adrenergic response in adult murine ventricular myocytes. ..
- Jin Y, Wu M. Requirement of Galphai in thymic homing and early T cell development. Mol Immunol. 2008;45:3401-10 pubmed publisher..Absence of either Galphai2 or Galphai3 significantly abrogated thymic homing, with an effect of Galphai3 being greater than that of Galphai2...
- Jin Y, Thompson B, Zhou Z, Fu Y, Birnbaumer L, Wu M. Reciprocal function of Galphai2 and Galphai3 in graft-versus-host disease. Eur J Immunol. 2008;38:1988-98 pubmed publisherThis study delineates specific functions of Galphai2 and Galphai3 in T cell mobilization during the development of graft-versus-host disease (GVHD) and reveals reciprocal effects of these two G proteins on the onset and morbidity of the ..
- 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..rate responses? Published findings using a variety of experimental approaches have implicated roles for Galphai2, Galphai3, and Galphao in parasympathetic signal transduction...
- Hwang I, Park C, Harrision K, Huang N, Kehrl J. Variations in Gnai2 and Rgs1 expression affect chemokine receptor signaling and the organization of secondary lymphoid organs. Genes Immun. 2010;11:384-96 pubmed publisher..Examination of B cells from mice with varying numbers of intact alleles of Ccr7, Rgs1, Gnai2, and Gnai3 provided the basis for these results...
- 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. ..
- 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
- Young A, Wang Y, Ahmedli N, Jiang M, Farber D. A constitutively active G?i3 protein corrects the abnormal retinal pigment epithelium phenotype of Oa1-/- mice. PLoS ONE. 2013;8:e76240 pubmed publisher..Our results show that a constitutively active G?i3 protein can by-pass the lack of Oa1 protein in Oa1-/- mice and consequently rescue the RPE melanosomal phenotype. ..
- Dizayee S, Kaestner S, Kuck F, Hein P, Klein C, Piekorz R, et al. G?i2- and G?i3-specific regulation of voltage-dependent L-type calcium channels in cardiomyocytes. PLoS ONE. 2011;6:e24979 pubmed publisher..In particular, loss of G?(i2) is reflected by alterations in channel kinetics and likely involves an impairment of the ERK1/2 signalling pathway. ..
- 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. ..
- 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. ..
- 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. ..
- Williams S, Ratliff L, Postiglione M, Knoblich J, Fuchs E. Par3-mInsc and G?i3 cooperate to promote oriented epidermal cell divisions through LGN. Nat Cell Biol. 2014;16:758-69 pubmed publisher..Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN...
- Devanathan V, Hagedorn I, KÃ¶hler D, Pexa K, Cherpokova D, Kraft P, et al. Platelet Gi protein GÎ±i2 is an essential mediator of thrombo-inflammatory organ damage in mice. Proc Natl Acad Sci U S A. 2015;112:6491-6 pubmed publisher..In conclusion, our data provide definitive evidence that platelet GÎ±(i2) not only controls hemostatic and thrombotic responses but also is critical for the development of ischemia/reperfusion injury in vivo. ..
- Siletti K, Tarchini B, Hudspeth A. Daple coordinates organ-wide and cell-intrinsic polarity to pattern inner-ear hair bundles. Proc Natl Acad Sci U S A. 2017;114:E11170-E11179 pubmed publisher..Our results suggest that the primary cilium or an associated structure influences the domain of cell-intrinsic signals that shape the hair bundle. Daple is therefore essential to orient and pattern sensory hair bundles. ..
- 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. ..
- 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. ..
- Wu T, Li Y, Huang D, Han F, Zhang Y, Zhang D, et al. Regulator of G-protein signaling 19 (RGS19) and its partner G?-inhibiting activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell death in L929 cells. PLoS ONE. 2014;9:e94634 pubmed publisher..We showed that RGS19 and its partner G?-inhibiting activity polypeptide 3 (GNAI3) are involved in zVAD-, but not TNF-, induced cell death...
- Kuwano Y, Adler M, Zhang H, Groisman A, Ley K. GÎ±i2 and GÎ±i3 Differentially Regulate Arrest from Flow and Chemotaxis in Mouse Neutrophils. J Immunol. 2016;196:3828-33 pubmed publisher..We conclude that GÎ±i2 controls arrest and GÎ±i3 controls transmigration and chemotaxis in response to chemokine stimulation of neutrophils. ..
- Duan S, Christe M, Milstone D, Mortensen R. Go but not Gi2 or Gi3 is required for muscarinic regulation of heart rate and heart rate variability in mice. Biochem Biophys Res Commun. 2007;357:139-43 pubmed..These differences in heart rate and HRV were not observed in alpha(i2)-null or alpha(i3)-null mice. Our findings establish an essential role for alpha(o) G protein in the anti-adrenergic effect of carbachol on heart rate regulation. ..
- Pero R, Borchers M, Spicher K, Ochkur S, Sikora L, Rao S, et al. Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation. Proc Natl Acad Sci U S A. 2007;104:4371-6 pubmed..Collectively, these data suggest that specific Galpha(i2)-mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation. ..
- Cadrin M, McFarlane Anderson N, Bégin Heick N. Identification and localization of G(i) alpha 3 in the clonal adipocyte cell lines HGFu and Ob17. Biochem Cell Biol. 1993;71:518-21 pubmed..These findings indicate a role for this subunit in vesicular traffic and are in agreement with the view of the adipocyte as a secretory cell. ..
- 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 22 and 20...
- Nagata Y, Oda M, Nakata H, Shozaki Y, Kozasa T, Todokoro K. A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes. Blood. 2001;97:3051-60 pubmed..Thus, RGS18 may play an important role in proliferation, differentiation, and/or migration of megakaryocytes. ..
- 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. ..
- Rock B, Xin L, Niederhuber J. 71.67 T lymphocyte activation is accompanied by the down-regulation of three G alpha genes. Cell Immunol. 1995;164:316-21 pubmed..These findings suggest that an important element in signal transduction through these G proteins in lymphocytes may include regulation of G alpha mRNA steady-state levels. ..
- May Simera H, Petralia R, Montcouquiol M, Wang Y, Szarama K, Liu Y, et al. Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea. Development. 2015;142:555-66 pubmed publisher..This could implicate these molecules in selective trafficking of membrane proteins upstream of cytoskeletal reorganization, and identifies new roles for cilia-related proteins in cochlear PCP. ..
- Miller K, Tan T, Welfare M, White S, Stark Z, Savarirayan R, et al. A mouse splice-site mutant and individuals with atypical chromosome 22q11.2 deletions demonstrate the crucial role for crkl in craniofacial and pharyngeal development. Mol Syndromol. 2014;5:276-86 pubmed publisher..These analyses demonstrate the central role of Crkl in regulating signalling events in the developing oropharyngeal complex and its potential to contribute to dysmorphology. ..
- Gaillard S, Lo Re L, Mantilleri A, Hepp R, Urien L, Malapert P, et al. GINIP, a GÎ±i-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. ..
- Sanada K, Tsai L. G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors. Cell. 2005;122:119-31 pubmed..Furthermore, our observations indicate that the cell-fate decision of daughter cells is coupled to mitotic-spindle orientation in progenitors. ..
- Hwang I, Park C, Luong T, Harrison K, Birnbaumer L, Kehrl J. The loss of Gnai2 and Gnai3 in B cells eliminates B lymphocyte compartments and leads to a hyper-IgM like syndrome. PLoS ONE. 2013;8:e72596 pubmed publisher..G?i2 and G?i3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function. These mice provide a worst case scenario of the consequences of losing chemoattractant receptor signaling in B cells. ..
- 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. ..
- Leyme A, Marivin A, Perez Gutierrez L, Nguyen L, Garcia Marcos M. Integrins activate trimeric G proteins via the nonreceptor protein GIV/Girdin. J Cell Biol. 2015;210:1165-84 pubmed publisher..Our discoveries delineate a novel mechanism by which integrin signaling is rewired during metastasis to result in increased tumor invasiveness. ..
- Abdelhamed Z, Natarajan S, Wheway G, Inglehearn C, Toomes C, Johnson C, et al. The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway. Dis Model Mech. 2015;8:527-41 pubmed publisher..Downstream therapeutic targeting of the Wnt5a-TMEM67-ROR2 axis might, therefore, reduce or prevent pulmonary hypoplasia in ciliopathies and other congenital conditions. ..
- Byrd K, Lough K, Patel J, Descovich C, Curtis T, Williams S. LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development. Development. 2016;143:2803-17 pubmed publisher..Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. ..
- Forge A, Taylor R, Dawson S, Lovett M, Jagger D. Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear. PLoS Genet. 2017;13:e1006692 pubmed publisher..The results suggest that SorCS2 plays a role upstream of the intrinsic polarity pathway and that there are differences between hair cell types in the deployment of the machinery that generates a precisely organised hair bundle. ..
- Huang N, Becker S, Boularan C, Kamenyeva O, Vural A, Hwang I, et al. Canonical and noncanonical g-protein signaling helps coordinate actin dynamics to promote macrophage phagocytosis of zymosan. Mol Cell Biol. 2014;34:4186-99 pubmed publisher..Our studies demonstrate that targeting heterotrimeric G-protein signaling offers opportunities to enhance or retard macrophage engulfment of phagocytic targets such as zymosan. ..
- Kohler D, Devanathan V, Bernardo de Oliveira Franz C, Eldh T, Novakovic A, Roth J, et al. G?i2- and G?i3-deficient mice display opposite severity of myocardial ischemia reperfusion injury. PLoS ONE. 2014;9:e98325 pubmed publisher..In conclusion, we demonstrate for the first time that the genetic ablation of G?i proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent. ..
- 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. ..
- 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...
- Ye C, Duan S, Milstone D, Mortensen R. G(o) controls the hyperpolarization-activated current in embryonic stem cell-derived cardiocytes. Am J Physiol Heart Circ Physiol. 2008;294:H979-85 pubmed..Our findings establish an essential role for G(o) in the antiadrenergic effect of muscarinic agent on I(f). ..
- Laliberte B, Wilson A, Nafisi H, Mao H, Zhou Y, Daigle M, et al. TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation. J Cell Physiol. 2010;225:865-74 pubmed publisher..The data suggest that G?i-TNFAIP8-mediated rescue of pre-oncogenic cells enhances progression to oncogenic transformation, providing a selective target to inhibit cellular transformation. ..
- 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. ..
- Boularan C, Hwang I, Kamenyeva O, Park C, Harrison K, Huang Z, et al. B Lymphocyte-Specific Loss of Ric-8A Results in a GÎ± Protein Deficit and Severe Humoral Immunodeficiency. J Immunol. 2015;195:2090-102 pubmed publisher..In B lymphocytes, Ric-8A is essential for normal GÎ± protein levels and is required for B cell differentiation, trafficking, and Ab responses. ..
- Farhy Tselnicker I, Tsemakhovich V, Rishal I, Kahanovitch U, Dessauer C, Dascal N. Dual regulation of G proteins and the G-protein-activated K+ channels by lithium. Proc Natl Acad Sci U S A. 2014;111:5018-23 pubmed publisher..Our findings link between Li(+), neuronal excitability, and both cellular and genetic targets of BPD: GPCRs, G proteins, and ion channels. ..
- 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
- Vural A, McQuiston T, Blumer J, Park C, Hwang I, Williams Bey Y, et al. Normal autophagic activity in macrophages from mice lacking G?i3, AGS3, or RGS19. PLoS ONE. 2013;8:e81886 pubmed publisher..LC3 processing and the formation of LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3(-/-), Gpsm1(-/-), or Rgs19(-/-) mice following amino acid starvation or Nigericin treatment...