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Vol. 17, No. 1, 2009
Issue release date: February 2009
Section title: Invited Review
Free Access
Neurosignals 2009;17:23–41

Molecular Mechanisms of Go Signaling

Jiang M. · Bajpayee N.S.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Calif., USA
email Corresponding Author

Dr. Meisheng Jiang

Department of Molecular and Medical Pharmacology

David Geffen School of Medicine, University of California Los Angeles

710 Westwood Plaza, Reed 3127, Los Angeles, CA 90095 (USA)

Tel. +1 310 794 7802, Fax +1 310 794 7380, E-Mail


  1. Birnbaumer L, Pohl SL, Rodbell M, Sundby F: The glucagon-sensitive adenylate cyclase system in plasma membranes of rat liver. VII. Hormonal stimulation: reversibility and dependence on concentration of free hormone. J Biol Chem 1972;247:2038–2043.
  2. Ross EM, Gilman AG: Resolution of some components of adenylate cyclase necessary for catalytic activity. J Biol Chem 1977;252:6966–6969.
  3. Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem 1987;56:615–649.
  4. Fung BK, Hurley JB, Stryer L: Flow of information in the light-triggered cyclic nucleotide cascade of vision. Proc Natl Acad Sci USA 1981;78:152–156.
  5. Moss J, Manganiello VC, Vaughan M: Substrate and effector specificity of a guanosine 3′,5′-monophosphate phosphodiesterase from rat liver. J Biol Chem 1977;252:5211–5215.
  6. Gill DM, Meren R: ADP ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci USA 1978;75:3050–3054.
  7. Cassel D, Pfeuffer T: Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc Natl Acad Sci USA 1978;75:2669–2673.
  8. Katada T, Amano T, Ui M: Modulation by islet-activating protein of adenylate cyclase activity in C6 glioma cells. J Biol Chem 1982;257:3739–3746.
  9. Katada T, Ui M: Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP ribosylation of a membrane protein. Proc Natl Acad Sci USA 1982;79:3129–3133.
  10. Codina J, Hildebrandt J, Iyengar R, Birnbaumer L, Sekura RD, Manclark CR: Pertussis toxin substrate, the putative Ni component of adenylyl cyclases, is an alpha beta heterodimer regulated by guanine nucleotide and magnesium. Proc Natl Acad Sci USA 1983;80:4276–4280.
  11. Bokoch GM, Katada T, Northup JK, Hewlett EL, Gilman AG: Identification of the predominant substrate for ADP ribosylation by islet-activating protein. J Biol Chem 1983;258:2072–2075.
  12. Neer EJ, Lok JM, Wolf LG: Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J Biol Chem 1984;259:14222–14229.
  13. Sternweis PC, Robishaw JD: Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem 1984;259:13806–13813.
  14. Milligan G, Klee WA: The inhibitory guanine nucleotide-binding protein (Ni) purified from bovine brain is a high affinity GTPase. J Biol Chem 1985;260:2057–2063.
  15. Itoh H, Kozasa T, Nagata S, Nakamura S, Katada T, Ui M, Iwai S, Ohtsuka E, Kawasaki H, Suzuki K, et al: Molecular cloning and sequence determination of cDNAs for alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. Proc Natl Acad Sci USA 1986;83:3776–3780.
  16. Ferguson KM, Higashijima T, Smigel MD, Gilman AG: The influence of bound GDP on the kinetics of guanine nucleotide binding to G proteins. J Biol Chem 1986;261:7393–7399.
  17. Strittmatter SM, Valenzuela D, Sudo Y, Linder ME, Fishman MC: An intracellular guanine nucleotide release protein for G0. GAP-43 stimulates isolated alpha subunits by a novel mechanism. J Biol Chem 1991;266:22465–22471.
  18. Strittmatter SM, Valenzuela D, Vartanian T, Sudo Y, Zuber MX, Fishman MC: Growth cone transduction: Go and GAP-43. J Cell Sci Suppl 1991;15:27–33.
  19. Cismowski MJ, Takesono A, Ma C, Lizano JS, Xie X, Fuernkranz H, Lanier SM, Duzic E: Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling. Nat Biotechnol 1999;17:878–883.
  20. Cismowski MJ, Ma C, Ribas C, Xie X, Spruyt M, Lizano JS, Lanier SM, Duzic E: Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration. J Biol Chem 2000;275:23421–23424.
  21. Kemppainen RJ, Behrend EN: Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. J Biol Chem 1998;273:3129–3131.
  22. Graham TE, Prossnitz ER, Dorin RI: Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases. J Biol Chem 2002;277:10876–10882.
  23. Takesono A, Zahner J, Blumer KJ, Nagao T, Kurose H: Negative regulation of alpha-2-adrenergic receptor-mediated Gi signalling by a novel pathway. Biochem J 1999;343 Pt 1:77–85.
  24. Siderovski DP, Diverse-Pierluissi M, De Vries L: The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor. Trends Biochem Sci 1999;24:340–341.
  25. De Vries L, Zheng B, Fischer T, Elenko E, Farquhar MG: The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 2000;40:235–271.
  26. Diverse-Pierluissi MA, Fischer T, Jordan JD, Schiff M, Ortiz DF, Farquhar MG, De Vries L: Regulators of G protein signaling proteins as determinants of the rate of desensitization of presynaptic calcium channels. J Biol Chem 1999;274:14490–14494.
  27. Xu X, Zeng W, Popov S, Berman DM, Davignon I, Yu K, Yowe D, Offermanns S, Muallem S, Wilkie TM: RGS proteins determine signaling specificity of Gq-coupled receptors. J Biol Chem 1999;274:3549–3556.
  28. Hoffmann M, Ward RJ, Cavalli A, Carr IC, Milligan G: Differential capacities of the RGS1, RGS16 and RGS-GAIP regulators of G protein signaling to enhance alpha-2A-adrenoreceptor agonist-stimulated GTPase activity of G(o1)alpha. J Neurochem 2001;78:797–806.
  29. Murtagh JJ Jr, Eddy R, Shows TB, Moss J, Vaughan M: Different forms of Go alpha mRNA arise by alternative splicing of transcripts from a single gene on human chromosome 16. Mol Cell Biol 1991;11:1146–1155.
  30. Jones DT, Reed RR: Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem 1987;262:14241–14249.
  31. Strathmann M, Wilkie TM, Simon MI: Alternative splicing produces transcripts encoding two forms of the alpha subunit of GTP-binding protein Go. Proc Natl Acad Sci USA 1990;87:6477–6481.
  32. Hsu WH, Rudolph U, Sanford J, Bertrand P, Olate J, Nelson C, Moss LG, Boyd AE, Codina J, Birnbaumer L: Molecular cloning of a novel splice variant of the alpha subunit of the mammalian Go protein. J Biol Chem 1990;265:11220–11226.
  33. Van Meurs KP, Angus CW, Lavu S, Kung HF, Czarnecki SK, Moss J, Vaughan M: Deduced amino acid sequence of bovine retinal Go alpha: similarities to other guanine nucleotide-binding proteins. Proc Natl Acad Sci USA 1987;84:3107–3111.
  34. Damodaran S, Dlugos CA, Wood TD, Rabin RA: Effects of chronic ethanol administration on brain protein levels: a proteomic investigation using 2-D DIGE system. Eur J Pharmacol 2006;547:75–82.
  35. Olate J, Martinez S, Purcell P, Jorquera H, Codina J, Birnbaumer L, Allende J: Molecular cloning and sequence determination of four different cDNA species coding for alpha-subunits of G proteins from Xenopus laevis oocytes. FEBS Lett 1990;268:27–31.
  36. Yoon J, Shortridge RD, Bloomquist BT, Schneuwly S, Perdew MH, Pak WL: Molecular characterization of Drosophila gene encoding G0 alpha subunit homolog. J Biol Chem 1989;264:18536–18543.
  37. De Sousa SM, Hoveland LL, Yarfitz S, Hurley JB: The Drosophila Go alpha-like G protein gene produces multiple transcripts and is expressed in the nervous system and in ovaries. J Biol Chem 1989;264:18544–18551.
  38. Thambi NC, Quan F, Wolfgang WJ, Spiegel A, Forte M: Immunological and molecular characterization of Go alpha-like proteins in the Drosophila central nervous system. J Biol Chem 1989;264:18552–18560.
  39. Lochrie MA, Mendel JE, Sternberg PW, Simon MI: Homologous and unique G protein alpha subunits in the nematode Caenorhabditis elegans. Cell Regul 1991;2:135–154.
  40. Miura N, Atsumi S, Tabunoki H, Sato R: Expression and localization of three G protein alpha subunits, Go, Gq, and Gs, in adult antennae of the silkmoth (Bombyx mori). J Comp Neurol 2005;485:143–152.
  41. Goldsmith P, Backlund PS Jr, Rossiter K, Carter A, Milligan G, Unson CG, Spiegel A: Purification of heterotrimeric GTP-binding proteins from brain: identification of a novel form of Go. Biochemistry 1988;27:7085–7090.
  42. Lang J: Purification and characterization of subforms of the guanine-nucleotide-binding proteins G alpha i and G alpha o. Eur J Biochem 1989;183:687–692.
  43. Scherer NM, Toro MJ, Entman ML, Birnbaumer L: G-protein distribution in canine cardiac sarcoplasmic reticulum and sarcolemma: comparison to rabbit skeletal muscle membranes and to brain and erythrocyte G-proteins. Arch Biochem Biophys 1987;259:431–440.
  44. Strathmann M, Simon MI: G protein diversity: a distinct class of alpha subunits is present in vertebrates and invertebrates. Proc Natl Acad Sci USA 1990;87:9113–9117.
  45. Tsukamoto T, Toyama R, Itoh H, Kozasa T, Matsuoka M, Kaziro Y: Structure of the human gene and two rat cDNAs encoding the alpha chain of GTP-binding regulatory protein Go: two different mRNAs are generated by alternative splicing. Proc Natl Acad Sci USA 1991;88:2974–2978.
  46. 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 USA 2001;98:3577–3582.
  47. Linder ME, Pang IH, Duronio RJ, Gordon JI, Sternweis PC, Gilman AG: Lipid modifications of G protein subunits. Myristoylation of Go alpha increases its affinity for beta gamma. J Biol Chem 1991;266:4654–4659.
  48. Mumby SM, Heukeroth RO, Gordon JI, Gilman AG: G-protein alpha-subunit expression, myristoylation, and membrane association in COS cells. Proc Natl Acad Sci USA 1990;87:728–732.
  49. Jones TL, Simonds WF, Merendino JJ Jr, Brann MR, Spiegel AM: Myristoylation of an inhibitory GTP-binding protein alpha subunit is essential for its membrane attachment. Proc Natl Acad Sci USA 1990;87:568–572.
  50. Gallego C, Gupta SK, Winitz S, Eisfelder BJ, Johnson GL: Myristoylation of the G alpha i2 polypeptide, a G protein alpha subunit, is required for its signaling and transformation functions. Proc Natl Acad Sci USA 1992;89:9695–9699.
  51. Linder ME, Middleton P, Hepler JR, Taussig R, Gilman AG, Mumby SM: Lipid modifications of G proteins: alpha subunits are palmitoylated. Proc Natl Acad Sci USA 1993;90:3675–3679.
  52. Mumby SM, Kleuss C, Gilman AG: Receptor regulation of G-protein palmitoylation. Proc Natl Acad Sci USA 1994;91:2800–2804.
  53. Barclay E, O’Reilly M, Milligan G: Activation of an alpha-2A-adrenoceptor-Galphao1 fusion protein dynamically regulates the palmitoylation status of the G protein but not of the receptor. Biochem J 2005;385:197–206.
  54. Busconi L, Boutin PM, Denker BM: N-terminal binding domain of Galpha subunits: involvement of amino acids 11–14 of Galphao in membrane attachment. Biochem J 1997;323:239–244.
  55. Chen CA, Manning DR: Regulation of G proteins by covalent modification. Oncogene 2001;20:1643–1652.
  56. Kobayashi I, Shibasaki H, Takahashi K, Kikkawa S, Ui M, Katada T: Purification of GTP-binding proteins from bovine brain membranes. Identification of heterogeneity of the alpha-subunit of Go proteins. FEBS Lett 1989;257:177–180.
  57. McIntire WE, Dingus J, Schey KL, Hildebrandt JD: Characterization of the major bovine brain Go alpha isoforms. Mapping the structural differences between the alpha subunit isoforms identifies a variable region of the protein involved in receptor interactions. J Biol Chem 1998;273:33135–33141.
  58. McIntire WE, Schey KL, Knapp DR, Hildebrandt JD: A major G protein alpha O isoform in bovine brain is deamidated at Asn346 and Asn347, residues involved in receptor coupling. Biochemistry 1998;37:14651–14658.
  59. Exner T, Jensen ON, Mann M, Kleuss C, Nurnberg B: Posttranslational modification of Galphao1 generates Galphao3, an abundant G protein in brain. Proc Natl Acad Sci USA 1999;96:1327–1332.
  60. McIntire WE, Dingus J, Wilcox MD, Hildebrandt JD: The relationship of G(o)alpha subunit deamidation to the tissue distribution, nucleotide binding properties, and betagamma dimer interactions of G(o)alpha subunit isoforms. J Neurochem 1999;73:633–640.
  61. Huff RM, Axton JM, Neer EJ: Physical and immunological characterization of a guanine nucleotide-binding protein purified from bovine cerebral cortex. J Biol Chem 1985;260:10864–10871.
  62. Vardi N: Alpha subunit of Go localizes in the dendritic tips of ON bipolar cells. J Comp Neurol 1998;395:43–52.
  63. Shinohara H, Kato K, Asano T: Differential localization of G proteins, Gi and Go, in the olfactory epithelium and the main olfactory bulb of the rat. Acta Anat (Basel) 1992;144:167–171.
  64. Homburger V, Brabet P, Audigier Y, Pantaloni C, Bockaert J, Rouot B: Immunological localization of the GTP-binding protein Go in different tissues of vertebrates and invertebrates. Mol Pharmacol 1987;31:313–319.
  65. Liang BT, Hellmich MR, Neer EJ, Galper JB: Development of muscarinic cholinergic inhibition of adenylate cyclase in embryonic chick heart. Its relationship to changes in the inhibitory guanine nucleotide regulatory protein. J Biol Chem 1986;261:9011–9021.
  66. Asano T, Kamiya N, Semba R, Kato K: Ontogeny of the GTP-binding protein Go in rat brain and heart. J Neurochem 1988;51:1711–1716.
  67. Milligan G, Tanfin Z, Goureau O, Unson C, Harbon S: Identification of both Gi2 and a novel, immunologically distinct, form of Go in rat myometrial membranes. FEBS Lett 1989;244:411–416.
  68. Wolf WP, Spicher K, Haase H, Schulze W: Immunocytochemical localization of the G-protein subunit, G(o) alpha, in rat heart. Implications for a role of G(o) alpha in secretion of cardiac hormones. J Mol Cell Cardiol 1998;30:1149–1162.
  69. Worley PF, Baraban JM, Van Dop C, Neer EJ, Snyder SH: Go, a guanine nucleotide-binding protein: immunohistochemical localization in rat brain resembles distribution of second messenger systems. Proc Natl Acad Sci USA 1986;83:4561–4565.
  70. Gabrion J, Brabet P, Nguyen Than Dao B, Homburger V, Dumuis A, Sebben M, Rouot B, Bockaert J: Ultrastructural localization of the GTP-binding protein Go in neurons. Cell Signal 1989;1:107–123.
  71. Galper JB, Klein W, Catterall WA: Muscarinic acetylcholine receptors in developing chick heart. J Biol Chem 1977;252:8692–8699.
  72. Luetje CW, Tietje KM, Christian JL, Nathanson NM: Differential tissue expression and developmental regulation of guanine nucleotide binding regulatory proteins and their messenger RNAs in rat heart. J Biol Chem 1988;263:13357–13365.
  73. Kawai Y, Arinze IJ: Differential localization and development-dependent expression of G-protein subunits, Go alpha and G beta, in rabbit heart. J Mol Cell Cardiol 1996;28:1555–1564.
  74. Mullaney I, Milligan G: Elevated levels of the guanine nucleotide binding protein, Go, are associated with differentiation of neuroblastoma × glioma hybrid cells. FEBS Lett 1989;244:113–118.
  75. Brabet P, Pantaloni C, Rodriguez M, Martinez J, Bockaert J, Homburger V: Neuroblastoma differentiation involves the expression of two isoforms of the alpha-subunit of Go. J Neurochem 1990;54:1310–1320.
  76. Brabet P, Pantaloni C, Bockaert J, Homburger V: Metabolism of two Go alpha isoforms in neuronal cells during differentiation. J Biol Chem 1991;266:12825–12828.
  77. Ben-Shlomo I, Yu Hsu S, Rauch R, Kowalski HW, Hsueh AJ: Signaling receptome: a genomic and evolutionary perspective of plasma membrane receptors involved in signal transduction. Sci STKE 2003;2003:RE9.

    External Resources

  78. Florio VA, Sternweis PC: Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins. J Biol Chem 1985;260:3477–3483.
  79. Kurose H, Katada T, Haga T, Haga K, Ichiyama A, Ui M: Functional interaction of purified muscarinic receptors with purified inhibitory guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles. J Biol Chem 1986;261:6423–6428.
  80. Ueda H, Harada H, Nozaki M, Katada T, Ui M, Satoh M, Takagi H: Reconstitution of rat brain mu opioid receptors with purified guanine nucleotide-binding regulatory proteins, Gi and Go. Proc Natl Acad Sci USA 1988;85:7013–7017.
  81. Lewis DL, Weight FF, Luini A: A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent calcium current by somatostatin in a pituitary cell line. Proc Natl Acad Sci USA 1986;83:9035–9039.
  82. Law SF, Manning D, Reisine T: Identification of the subunits of GTP-binding proteins coupled to somatostatin receptors. J Biol Chem 1991;266:17885–17897.
  83. Hescheler J, Rosenthal W, Trautwein W, Schultz G: The GTP-binding protein, Go, regulates neuronal calcium channels. Nature 1987;325:445–447.
  84. Ewald DA, Sternweis PC, Miller RJ: Guanine nucleotide-binding protein Go-induced coupling of neuropeptide Y receptors to Ca2+ channels in sensory neurons. Proc Natl Acad Sci USA 1988;85:3633–3637.
  85. Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B: Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 1991;353:43–48.
  86. Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B: Different beta-subunits determine G-protein interaction with transmembrane receptors. Nature 1992;358:424–426.
  87. Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B: Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins. Science 1993;259:832–834.
  88. Jiang M, Boulay G, Spicher K, Peyton MJ, Brabet P, Birnbaumer L, Rudolph U: Inactivation of the G alpha i2 and G alpha o genes by homologous recombination. Receptors Channels 1997;5:187–192.
  89. Jiang M, Gold MS, Boulay G, Spicher K, Peyton M, Brabet P, Srinivasan Y, Rudolph U, Ellison G, Birnbaumer L: Multiple neurological abnormalities in mice deficient in the G protein Go. Proc Natl Acad Sci USA 1998;95:3269–3274.
  90. Valenzuela D, Han X, Mende U, Fankhauser C, Mashimo H, Huang P, Pfeffer J, Neer EJ, Fishman MC: G alpha(o) is necessary for muscarinic regulation of Ca2+ channels in mouse heart. Proc Natl Acad Sci USA 1997;94:1727–1732.
  91. Dunlap K, Fischbach GD: Neurotransmitters decrease the calcium component of sensory neurone action potentials. Nature 1978;276:837–839.
  92. Dunlap K, Fischbach GD: Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol 1981;317:519–535.
  93. Holz GG 4th, Rane SG, Dunlap K: GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels. Nature 1986;319:670–672.
  94. Scott RH, Dolphin AC: Regulation of calcium currents by a GTP analogue: potentiation of (–)-baclofen-mediated inhibition. Neurosci Lett 1986;69:59–64.
  95. Hille B: Modulation of ion-channel function by G-protein-coupled receptors. Trends Neurosci 1994;17:531–536.
  96. Ewald DA, Pang IH, Sternweis PC, Miller RJ: Differential G protein-mediated coupling of neurotransmitter receptors to Ca2+ channels in rat dorsal root ganglion neurons in vitro. Neuron 1989;2:1185–1193.
  97. Campbell V, Berrow N, Dolphin AC: GABAB receptor modulation of Ca2+ currents in rat sensory neurones by the G protein G(0): antisense oligonucleotide studies. J Physiol 1993;470:1–11.
  98. Caulfield MP, Jones S, Vallis Y, Buckley NJ, Kim GD, Milligan G, Brown DA: Muscarinic M-current inhibition via G alpha q/11 and alpha-adrenoceptor inhibition of Ca2+ current via G alpha o in rat sympathetic neurones. J Physiol 1994;477:415–422.
  99. Jan LY, Jan YN: How might the diversity of potassium channels be generated? Trends Neurosci 1990;13:415–419.
  100. Pfaffinger PJ, Martin JM, Hunter DD, Nathanson NM, Hille B: GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature 1985;317:536–538.
  101. Andrade R, Malenka RC, Nicoll RA: A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 1986;234:1261–1265.
  102. VanDongen AM, Codina J, Olate J, Mattera R, Joho R, Birnbaumer L, Brown AM: Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go. Science 1988;242:1433–1437.
  103. Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE: The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature 1987;325:321–326.
  104. Wickman KD, Iniguez-Lluhl JA, Davenport PA, Taussig R, Krapivinsky GB, Linder ME, Gilman AG, Clapham DE: Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature 1994;368:255–257.
  105. Reuveny E, Slesinger PA, Inglese J, Morales JM, Iniguez-Lluhi JA, Lefkowitz RJ, Bourne HR, Jan YN, Jan LY: Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. Nature 1994;370:143–146.
  106. Huang CL, Jan YN, Jan LY: Binding of the G protein betagamma subunit to multiple regions of G protein-gated inward-rectifying K+ channels. FEBS Lett 1997;405:291–298.
  107. Lei Q, Jones MB, Talley EM, Schrier AD, McIntire WE, Garrison JC, Bayliss DA: Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein beta gamma subunits. Proc Natl Acad Sci USA 2000;97:9771–9776.
  108. Peleg S, Varon D, Ivanina T, Dessauer CW, Dascal N: G-alpha-i controls the gating of the G protein-activated K+ channel, GIRK. Neuron 2002;33:87–99.
  109. Cohen-Armon M, Sokolovsky M: Depolarization-induced changes in the muscarinic receptor in rat brain and heart are mediated by pertussis-toxin-sensitive G-proteins. J Biol Chem 1991;266:2595–2605.
  110. Cohen-Armon M, Sokolovsky M: Evidence for involvement of the voltage-dependent Na+ channel gating in depolarization-induced activation of G-proteins. J Biol Chem 1993;268:9824–9838.
  111. Anis Y, Nurnberg B, Visochek L, Reiss N, Naor Z, Cohen-Armon M: Activation of Go-proteins by membrane depolarization traced by in situ photoaffinity labeling of galphao-proteins with [α32P]GTP-azidoanilide. J Biol Chem 1999;274:7431–7440.
  112. Komwatana P, Dinudom A, Young JA, Cook DI: Cytosolic Na+ controls and epithelial Na+ channel via the Go guanine nucleotide-binding regulatory protein. Proc Natl Acad Sci USA 1996;93:8107–8111.
  113. Komwatana P, Dinudom A, Young JA, Cook DI: Activators of epithelial Na+ channels inhibit cytosolic feedback control. Evidence for the existence of a G protein-coupled receptor for cytosolic Na+. J Membr Biol 1998;162:225–232.
  114. Katada T, Oinuma M, Ui M: Two guanine nucleotide-binding proteins in rat brain serving as the specific substrate of islet- activating protein, pertussis toxin. Interaction of the alpha-subunits with beta gamma-subunits in development of their biological activities. J Biol Chem 1986;261:8182–8191.
  115. Wong YH, Conklin BR, Bourne HR: Gz-mediated hormonal inhibition of cyclic AMP accumulation. Science 1992;255:339–342.
  116. Kobayashi I, Shibasaki H, Takahashi K, Tohyama K, Kurachi Y, Ito H, Ui M, Katada T: Purification and characterization of five different alpha subunits of guanine-nucleotide-binding proteins in bovine brain membranes. Their physiological properties concerning the activities of adenylate cyclase and atrial muscarinic K+ channels. Eur J Biochem 1990;191:499–506.
  117. Ghil S, Choi JM, Kim SS, Lee YD, Liao Y, Birnbaumer L, Suh-Kim H: Compartmentalization of protein kinase A signaling by the heterotrimeric G protein Go. Proc Natl Acad Sci USA 2006;103:19158–19163.
  118. Mendel JE, Korswagen HC, Liu KS, Hajdu-Cronin YM, Simon MI, Plasterk RH, Sternberg PW: Participation of the protein Go in multiple aspects of behavior in C. elegans. Science 1995;267:1652–1655.
  119. Segalat L, Elkes DA, Kaplan JM: Modulation of serotonin-controlled behaviors by Go in Caenorhabditis elegans. Science 1995;267:1648–1651.
  120. Miller KG, Emerson MD, Rand JB: Goalpha and diacylglycerol kinase negatively regulate the Gqalpha pathway in C. elegans. Neuron 1999;24:323–333.
  121. Nurrish S, Segalat L, Kaplan JM: Serotonin inhibition of synaptic transmission: Galpha(0) decreases the abundance of UNC-13 at release sites. Neuron 1999;24:231–242.
  122. Matsuki M, Kunitomo H, Iino Y: Goalpha regulates olfactory adaptation by antagonizing Gqalpha-DAG signaling in Caenorhabditis elegans. Proc Natl Acad Sci USA 2006;103:1112–1117.
  123. Mendel J: Go directly (or indirectly) to Gq. Neuron 1999;24:287–288.
  124. Kroll SD, Chen J, De Vivo M, Carty DJ, Buku A, Premont RT, Iyengar R: The Q205LGo-alpha subunit expressed in NIH-3T3 cells induces transformation. J Biol Chem 1992;267:23183–23188.
  125. Kroll SD, Omri G, Landau EM, Iyengar R: Activated alpha subunit of Go protein induces oocyte maturation. Proc Natl Acad Sci USA 1991;88:5182–5186.
  126. Baffy G, Yang L, Raj S, Manning DR, Williamson JR: G protein coupling to the thrombin receptor in Chinese hamster lung fibroblasts. J Biol Chem 1994;269:8483–8487.
  127. Van Biesen T, Hawes BE, Raymond JR, Luttrell LM, Koch WJ, Lefkowitz RJ: G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism. J Biol Chem 1996;271:1266–1269.
  128. Jordan JD, Carey KD, Stork PJ, Iyengar R: Modulation of rap activity by direct interaction of Galpha(o) with Rap1 GTPase-activating protein. J Biol Chem 1999;274:21507–21510.
  129. Ram PT, Horvath CM, Iyengar R: Stat3-mediated transformation of NIH-3T3 cells by the constitutively active Q205L Galphao protein. Science 2000;287:142–144.
  130. Jordan JD, He JC, Eungdamrong NJ, Gomes I, Ali W, Nguyen T, Bivona TG, Philips MR, Devi LA, Iyengar R: Cannabinoid receptor-induced neurite outgrowth is mediated by Rap1 activation through G(alpha)o/i-triggered proteasomal degradation of Rap1GAPII. J Biol Chem 2005;280:11413–11421.
  131. He JC, Gomes I, Nguyen T, Jayaram G, Ram PT, Devi LA, Iyengar R: The G alpha(o/i)-coupled cannabinoid receptor-mediated neurite outgrowth involves Rap regulation of Src and Stat3. J Biol Chem 2005;280:33426–33434.
  132. Antonelli V, Bernasconi F, Wong YH, Vallar L: Activation of B-Raf and regulation of the mitogen-activated protein kinase pathway by the G(o) alpha chain. Mol Biol Cell 2000;11:1129–1142.
  133. Bernasconi F, Malgaroli A, Vallar L: Independent regulation of Rap1 and mitogen-activated protein kinase by the alpha chain of Go. Neurosignals 2006;15:180–189.
  134. Crespo P, Xu N, Simonds WF, Gutkind JS: Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. Nature 1994;369:418–420.
  135. Gutkind JS: The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades. J Biol Chem 1998;273:1839–1842.
  136. Toutant M, Aunis D, Bockaert J, Homburger V, Rouot B: Presence of three pertussis toxin substrates and Go alpha immunoreactivity in both plasma and granule membranes of chromaffin cells. FEBS Lett 1987;215:339–344.
  137. Lang J, Nishimoto I, Okamoto T, Regazzi R, Kiraly C, Weller U, Wollheim CB: Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits. EMBO J 1995;14:3635–3644.
  138. Gasman S, Chasserot-Golaz S, Popoff MR, Aunis D, Bader MF: Trimeric G proteins control exocytosis in chromaffin cells. Go regulates the peripheral actin network and catecholamine secretion by a mechanism involving the small GTP-binding protein Rho. J Biol Chem 1997;272:20564–20571.
  139. Vitale N, Gensse M, Chasserot-Golaz S, Aunis D, Bader MF: Trimeric G proteins control regulated exocytosis in bovine chromaffin cells: sequential involvement of Go associated with secretory granules and Gi3 bound to the plasma membrane. Eur J Neurosci 1996;8:1275–1285.
  140. Gasman S, Chasserot-Golaz S, Hubert P, Aunis D, Bader MF: Identification of a potential effector pathway for the trimeric Go protein associated with secretory granules. Go stimulates a granule-bound phosphatidylinositol 4-kinase by activating RhoA in chromaffin cells. J Biol Chem 1998;273:16913–16920.
  141. Ahnert-Hilger G, Schafer T, Spicher K, Grund C, Schultz G, Wiedenmann B: Detection of G-protein heterotrimers on large dense core and small synaptic vesicles of neuroendocrine and neuronal cells. Eur J Cell Biol 1994;65:26–38.
  142. Ahnert-Hilger G, Nurnberg B, Exner T, Schafer T, Jahn R: The heterotrimeric G protein Go2 regulates catecholamine uptake by secretory vesicles. EMBO J 1998;17:406–413.
  143. Holtje M, von Jagow B, Pahner I, Lautenschlager M, Hortnagl H, Nurnberg B, Jahn R, Ahnert-Hilger G: The neuronal monoamine transporter VMAT2 is regulated by the trimeric GTPase Go(2). J Neurosci 2000;20:2131–2141.
  144. Winter S, Brunk I, Walther DJ, Holtje M, Jiang M, Peter JU, Takamori S, Jahn R, Birnbaumer L, Ahnert-Hilger G: Galphao2 regulates vesicular glutamate transporter activity by changing its chloride dependence. J Neurosci 2005;25:4672–4680.
  145. Holtje M, Hofmann F, Lux R, Veh RW, Just I, Ahnert-Hilger G: Glutamate uptake and release by astrocytes is enhanced by Clostridium botulinum C3 protein. J Biol Chem 2008;283:9289–9299.
  146. Strittmatter SM, Valenzuela D, Kennedy TE, Neer EJ, Fishman MC: G0 is a major growth cone protein subject to regulation by GAP-43. Nature 1990;344:836–841.
  147. Meiri KF, Pfenninger KH, Willard MB: Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA 1986;83:3537–3541.
  148. Skene JH, Jacobson RD, Snipes GJ, McGuire CB, Norden JJ, Freeman JA: A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes. Science 1986;233:783–786.
  149. Benowitz LI, Shashoua VE, Yoon MG: Specific changes in rapidly transported proteins during regeneration of the goldfish optic nerve. J Neurosci 1981;1:300–307.
  150. Skene JH, Willard M: Changes in axonally transported proteins during axon regeneration in toad retinal ganglion cells. J Cell Biol 1981;89:86–95.
  151. Strittmatter SM, Fishman MC: The neuronal growth cone as a specialized transduction system. Bioessays 1991;13:127–134.
  152. Strittmatter SM, Fishman MC, Zhu XP: Activated mutants of the alpha subunit of G(o) promote an increased number of neurites per cell. J Neurosci 1994;14:2327–2338.
  153. Xie R, Li L, Goshima Y, Strittmatter SM: An activated mutant of the alpha subunit of G(o) increases neurite outgrowth via protein kinase C. Brain Res Dev Brain Res 1995;87:77–86.
  154. Kindt KS, Tam T, Whiteman S, Schafer WR: Serotonin promotes G(o)-dependent neuronal migration in Caenorhabditis elegans. Curr Biol 2002;12:1738–1747.
  155. Horgan AM, Copenhaver PF: G protein-mediated inhibition of neuronal migration requires calcium influx. J Neurosci 1998;18:4189–4200.
  156. Zheng JQ, Poo MM: Calcium signaling in neuronal motility. Annu Rev Cell Dev Biol 2007;23:375–404.
  157. Guillen A, Semeriva M, Bockaert J, Homburger V: The transduction signalling protein Go during embryonic development of Drosophila melanogaster. Cell Signal 1991;3:341–352.
  158. Wolfgang WJ, Quan F, Thambi N, Forte M: Restricted spatial and temporal expression of G-protein alpha subunits during Drosophila embryogenesis. Development 1991;113:527–538.
  159. Guillen A, Jallon JM, Fehrentz JA, Pantaloni C, Bockaert J, Homburger V: A Go-like protein in Drosophila melanogaster and its expression in memory mutants. Embo J 1990;9:1449–1455.
  160. Ferris J, Ge H, Liu L, Roman G: G(o) signaling is required for Drosophila associative learning. Nat Neurosci 2006;9:1036–1040.
  161. Katanaev VL, Ponzielli R, Semeriva M, Tomlinson A: Trimeric G protein-dependent frizzled signaling in Drosophila. Cell 2005;120:111–122.
  162. Katanaev VL, Tomlinson A: Dual roles for the trimeric G protein Go in asymmetric cell division in Drosophila. Proc Natl Acad Sci USA 2006;103:6524–6529.
  163. Brouillet E, Trembleau A, Galanaud D, Volovitch M, Bouillot C, Valenza C, Prochiantz A, Allinquant B: The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction. J Neurosci 1999;19:1717–1727.
  164. Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Okamoto T, Murayama Y, Ogata E: Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o). Nature 1993;362:75–79.
  165. Okamoto T, Takeda S, Giambarella U, Murayama Y, Matsui T, Katada T, Matsuura Y, Nishimoto I: Intrinsic signaling function of APP as a novel target of three V642 mutations linked to familial Alzheimer’s disease. Embo J 1996;15:3769–3777.
  166. Yamatsuji T, Okamoto T, Takeda S, Murayama Y, Tanaka N, Nishimoto I: Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype. Embo J 1996;15:498–509.
  167. Zhao B, Chrest FJ, Horton WE Jr, Sisodia SS, Kusiak JW: Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells. J Neurosci Res 1997;47:253–263.
  168. Giambarella U, Yamatsuji T, Okamoto T, Matsui T, Ikezu T, Murayama Y, Levine MA, Katz A, Gautam N, Nishimoto I: G protein betagamma complex-mediated apoptosis by familial Alzheimer’s disease mutant of APP. EMBO J 1997;16:4897–4907.
  169. McPhie DL, Coopersmith R, Hines-Peralta A, Chen Y, Ivins KJ, Manly SP, Kozlowski MR, Neve KA, Neve RL: DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21-activated kinase PAK3. J Neurosci 2003;23:6914–6927.
  170. Smine A, Xu X, Nishiyama K, Katada T, Gambetti P, Yadav SP, Wu X, Shi YC, Yasuhara S, Homburger V, Okamoto T: Regulation of brain G-protein go by Alzheimer’s disease gene presenilin-1. J Biol Chem 1998;273:16281–16288.
  171. Wolozin B, Iwasaki K, Vito P, Ganjei JK, Lacana E, Sunderland T, Zhao B, Kusiak JW, Wasco W, D’Adamio L: Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 1996;274:1710–1713.
  172. Roth KA: Caspases, apoptosis, and Alzheimer disease: causation, correlation, and confusion. J Neuropathol Exp Neurol 2001;60:829–838.
  173. Bozzi Y, Borrelli E: Dopamine in neurotoxicity and neuroprotection: what do D2 receptors have to do with it? Trends Neurosci 2006;29:167–174.
  174. Okada F, Crow TJ, Roberts GW: G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. J Neural Transm Gen Sect 1990;79:227–234.
  175. Okada F, Crow TJ, Roberts GW: G proteins (Gi, Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change. J Neural Transm Gen Sect 1991;84:147–153.
  176. Okada F, Tokumitsu Y, Takahashi N, Crow TJ, Roberts GW: Reduced concentrations of the alpha-subunit of GTP-binding protein Go in schizophrenic brain. J Neural Transm Gen Sect 1994;95:95–104.
  177. Yang CQ, Kitamura N, Nishino N, Shirakawa O, Nakai H: Isotype-specific G protein abnormalities in the left superior temporal cortex and limbic structures of patients with chronic schizophrenia. Biol Psychiatry 1998;43:12–19.
  178. Tani M, Mui K, Minami Y, Kiriike N: Association of a GTP-binding protein Go alpha subunit mutation with schizophrenia. Mol Psychiatry 2001;6:359.
  179. Schiller PH: The ON and OFF channels of the visual system. Trends Neurosci 1992;15:86–92.
  180. Nakajima Y, Iwakabe H, Akazawa C, Nawa H, Shigemoto R, Mizuno N, Nakanishi S: Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. J Biol Chem 1993;268:11868–11873.
  181. Masu M, Iwakabe H, Tagawa Y, Miyoshi T, Yamashita M, Fukuda Y, Sasaki H, Hiroi K, Nakamura Y, Shigemoto R, et al: Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 1995;80:757–765.
  182. Dhingra A, Lyubarsky A, Jiang M, Pugh EN Jr, Birnbaumer L, Sterling P, Vardi N: The light response of ON bipolar neurons requires G(alpha)o. J Neurosci 2000;20:9053–9058.
  183. Dhingra A, Jiang M, Wang TL, Lyubarsky A, Savchenko A, Bar-Yehuda T, Sterling P, Birnbaumer L, Vardi N: Light response of retinal ON bipolar cells requires a specific splice variant of Galpha(o). J Neurosci 2002;22:4878–4884.
  184. Duan SZ, Christe M, Milstone DS, Mortensen RM: 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;357:139–143.
  185. Zhu M, Gach AA, Liu G, Xu X, Lim CC, Zhang JX, Mao L, Chuprun K, Koch WJ, Liao R, Koren G, Blaxall BC, Mende U: Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G(alpha)o* protein. Am J Physiol 2008;294:H1335–H1347.