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Part of the book series: Subcellular Biochemistry ((SCBI,volume 63))

Abstract

The classical view of heterotrimeric G protein signaling places G ­proteins at the cytoplasmic surface of the cell’s plasma membrane where they are activated by an appropriate G protein-coupled receptor. Once activated, the GTP-bound Gα and the free Gβγ are able to regulate plasma membrane-localized effectors, such as adenylyl cyclase, phospholipase C-β, RhoGEFs and ion channels. Hydrolysis of GTP by the Gα subunit returns the G protein to the inactive Gαβγ heterotrimer. Although all of these events in the G protein cycle can be restricted to the cytoplasmic surface of the plasma membrane, G protein localization is dynamic. Thus, it has become increasingly clear that G proteins are able to move to diverse subcellular locations where they perform non-canonical signaling functions. This chapter will highlight our current understanding of trafficking pathways that target newly synthesized G proteins to the plasma membrane, activation-induced and reversible translocation of G proteins from the plasma membrane to intracellular locations, and constitutive trafficking of G proteins.

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References

  • Akgoz M, Kalyanaraman V, Gautam N (2004) Receptor-mediated reversible translocation of the G protein betagamma complex from the plasma membrane to the Golgi complex. J Biol Chem 279(49):51541–51544

    Article  PubMed  CAS  Google Scholar 

  • Akgoz M, Kalyanaraman V, Gautam N (2006) G protein betagamma complex translocation from plasma membrane to Golgi complex is influenced by receptor gamma subunit interaction. Cell Signal 18(10):1758–1768

    Article  PubMed  CAS  Google Scholar 

  • Allen JA, Yu JZ, Donati RJ, Rasenick MM (2005) Beta-adrenergic receptor stimulation promotes G alpha s internalization through lipid rafts: a study in living cells. Mol Pharmacol 67(5):1493–1504

    Article  PubMed  CAS  Google Scholar 

  • Artemyev NO (2008) Light-dependent compartmentalization of transducin in rod photoreceptors. Mol Neurobiol 37(1):44–51. doi:10.1007/s12035-008-8015-2

    Article  PubMed  CAS  Google Scholar 

  • Azpiazu I, Akgoz M, Kalyanaraman V, Gautam N (2006) G protein betagamma11 complex translocation is induced by Gi, Gq and Gs coupling receptors and is regulated by the alpha subunit type. Cell Signal 18(8):1190–1200

    Article  PubMed  CAS  Google Scholar 

  • Balbis A, Parmar A, Wang Y, Baquiran G, Posner BI (2007) Compartmentalization of signaling-competent epidermal growth factor receptors in endosomes. Endocrinology 148(6):2944–2954. doi:10.1210/en.2006-1674, pii:en.2006-1674

    Article  PubMed  CAS  Google Scholar 

  • Bereta G, Palczewski K (2011) Heterogeneous N-terminal acylation of retinal proteins results from the retina’s unusual lipid metabolism. Biochemistry 50(18):3764–3776. doi:10.1021/bi200245t

    Article  PubMed  CAS  Google Scholar 

  • Bhamre S, Wang HY, Friedman E (1998) Serotonin-mediated palmitoylation and depalmitoylation of G alpha proteins in rat brain cortical membranes. J Pharmacol Exp Ther 286(3):1482–1489

    PubMed  CAS  Google Scholar 

  • Bhattacharyya R, Wedegaertner PB (2000) Galpha 13 requires palmitoylation for plasma membrane localization, Rho-dependent signaling, and promotion of p115-RhoGEF membrane binding. J Biol Chem 275(20):14992–14999

    Article  PubMed  CAS  Google Scholar 

  • Calvert PD, Strissel KJ, Schiesser WE, Pugh EN Jr, Arshavsky VY (2006) Light-driven translocation of signaling proteins in vertebrate photoreceptors. Trends Cell Biol 16(11):560–568. doi:10.1016/j.tcb.2006.09.001, pii:S0962-8924(06)00237-6

    Article  PubMed  CAS  Google Scholar 

  • Chen CA, Manning DR (2000) Regulation of galpha i palmitoylation by activation of the 5-hydroxytryptamine-1A receptor. J Biol Chem 275(31):23516–23522

    Article  PubMed  CAS  Google Scholar 

  • Chisari M, Saini DK, Kalyanaraman V, Gautam N (2007) Shuttling of G protein subunits between the plasma membrane and intracellular membranes. J Biol Chem 282(33):24092–24098

    Article  PubMed  CAS  Google Scholar 

  • Chisari M, Saini DK, Cho JH, Kalyanaraman V, Gautam N (2009) G protein subunit dissociation and translocation regulate cellular response to receptor stimulation. PLoS One 4(11):e7797. doi:10.1371/journal.pone.0007797

    Article  PubMed  CAS  Google Scholar 

  • Cronin MA, Diao F, Tsunoda S (2004) Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC. J Cell Sci 117(Pt 20):4797–4806

    Article  PubMed  CAS  Google Scholar 

  • Crouthamel M, Thiyagarajan MM, Evanko DS, Wedegaertner PB (2008) N-terminal polybasic motifs are required for plasma membrane localization of Galpha(s) and Galpha(q). Cell Signal 20(10):1900–1910

    Article  PubMed  CAS  Google Scholar 

  • Crouthamel M, Abankwa D, Zhang L, DiLizio C, Manning DR, Hancock JF, Wedegaertner PB (2010) An N-terminal polybasic motif of Galphaq is required for signaling and influences membrane nanodomain distribution. Mol Pharmacol 78(4):767–777. doi:10.1124/mol.110.066340, pii:mol.110.066340

    Article  PubMed  CAS  Google Scholar 

  • David NB, Martin CA, Segalen M, Rosenfeld F, Schweisguth F, Bellaiche Y (2005) Drosophila Ric-8 regulates Galphai cortical localization to promote Galphai-dependent planar orientation of the mitotic spindle during asymmetric cell division. Nat Cell Biol 7(11):1083–1090. doi:10.1038/ncb1319, pii:ncb1319

    Article  PubMed  CAS  Google Scholar 

  • Degtyarev MY, Spiegel AM, Jones TL (1993) Increased palmitoylation of the Gs protein alpha subunit after activation by the beta-adrenergic receptor or cholera toxin. J Biol Chem 268(32):23769–23772

    PubMed  CAS  Google Scholar 

  • Diaz Anel AM (2007) Phospholipase C beta3 is a key component in the Gbetagamma/PKCeta/PKD-mediated regulation of trans-Golgi network to plasma membrane transport. Biochem J 406(1):157–165

    Article  PubMed  CAS  Google Scholar 

  • Diaz Anel AM, Malhotra V (2005) PKCeta is required for beta1gamma2/beta3gamma2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus. J Cell Biol 169(1):83–91

    Article  PubMed  CAS  Google Scholar 

  • Dorsam RT, Gutkind JS (2007) G-protein-coupled receptors and cancer. Nat Rev Cancer 7(2):79–94. doi:10.1038/nrc2069, pii:nrc2069

    Article  PubMed  CAS  Google Scholar 

  • Drmota T, Novotny J, Kim GD, Eidne KA, Milligan G, Svoboda P (1998) Agonist-induced internalization of the G protein G11alpha and thyrotropin-releasing hormone receptors proceed on different time scales. J Biol Chem 273(34):21699–21707

    Article  PubMed  CAS  Google Scholar 

  • Drmota T, Novotny J, Gould GW, Svoboda P, Milligan G (1999) Visualization of distinct patterns of subcellular redistribution of the thyrotropin-releasing hormone receptor-1 and gqalpha /G11alpha induced by agonist stimulation. Biochem J 340(Pt 2):529–538

    Article  PubMed  CAS  Google Scholar 

  • Duncan JA, Gilman AG (1998) A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). J Biol Chem 273(25):15830–15837

    Article  PubMed  CAS  Google Scholar 

  • Duncan JA, Gilman AG (2002) Characterization of Saccharomyces cerevisiae acyl-protein thioesterase 1, the enzyme responsible for G protein alpha subunit deacylation in vivo. J Biol Chem 277(35):31740–31752

    Article  PubMed  CAS  Google Scholar 

  • Dunphy JT, Linder ME (1998) Signalling functions of protein palmitoylation. Biochim Biophys Acta 1436(1–2):245–261

    PubMed  CAS  Google Scholar 

  • Dupre DJ, Robitaille M, Ethier N, Villeneuve LR, Mamarbachi AM, Hebert TE (2006) Seven transmembrane receptor core signalling complexes are assembled prior to plasma membrane trafficking. J Biol Chem 281(45):34561–34573

    Article  PubMed  CAS  Google Scholar 

  • Dupre DJ, Robitaille M, Richer M, Ethier N, Mamarbachi AM, Hebert TE (2007) Dopamine receptor-interacting protein 78 acts as a molecular chaperone for Ggamma subunits before assembly with Gbeta. J Biol Chem 282(18):13703–13715. doi:10.1074/jbc.M608846200, pii:M608846200

    Article  PubMed  CAS  Google Scholar 

  • Dupre DJ, Robitaille M, Rebois RV, Hebert TE (2009) The role of Gbetagamma subunits in the organization, assembly, and function of GPCR signaling complexes. Annu Rev Pharmacol Toxicol 49:31–56

    Article  PubMed  CAS  Google Scholar 

  • Elia N, Frechter S, Gedi Y, Minke B, Selinger Z (2005) Excess of Gbetae over Gqalphae in vivo prevents dark, spontaneous activity of Drosophila photoreceptors. J Cell Biol 171(3):517–526. doi:10.1083/jcb.200506082, pii:jcb.200506082

    Article  PubMed  CAS  Google Scholar 

  • Evanko DS, Thiyagarajan MM, Wedegaertner PB (2000) Interaction with Gbetagamma is required for membrane targeting and palmitoylation of Galpha(s) and Galpha(q). J Biol Chem 275(2):1327–1336

    Article  PubMed  CAS  Google Scholar 

  • Evanko DS, Thiyagarajan MM, Siderovski DP, Wedegaertner PB (2001) Gbeta gamma isoforms selectively rescue plasma membrane localization and palmitoylation of mutant Galphas and Galphaq. J Biol Chem 276(26):23945–23953

    Article  PubMed  CAS  Google Scholar 

  • Fishburn CS, Herzmark P, Morales J, Bourne HR (1999) Gbetagamma and palmitate target newly synthesized Galphaz to the plasma membrane. J Biol Chem 274(26):18793–18800

    Article  PubMed  CAS  Google Scholar 

  • Fishburn CS, Pollitt SK, Bourne HR (2000) Localization of a peripheral membrane protein: G beta gamma targets G alpha(z). Proc Natl Acad Sci USA 97(3):1085–1090

    Article  PubMed  CAS  Google Scholar 

  • Frechter S, Elia N, Tzarfaty V, Selinger Z, Minke B (2007) Translocation of Gq alpha mediates long-term adaptation in Drosophila photoreceptors. J Neurosci 27(21):5571–5583. doi:10.1523/JNEUROSCI.0310-07.2007, pii:27/21/5571

    Article  PubMed  CAS  Google Scholar 

  • Gabay M, Pinter ME, Wright FA, Chan P, Murphy AJ, Valenzuela DM, Yancopoulos GD, Tall GG (2011) Ric-8 proteins are molecular chaperones that direct nascent G protein alpha subunit membrane association. Sci Signal 4(200):ra79. doi:10.1126/scisignal.2002223, pii:4/200/ra79

    Article  PubMed  CAS  Google Scholar 

  • Galbiati F, Guzzi F, Magee AI, Milligan G, Parenti M (1994) N-terminal fatty acylation of the alpha-subunit of the G-protein Gi1: only the myristoylated protein is a substrate for palmitoylation. Biochem J 303(Pt 3):697–700

    PubMed  CAS  Google Scholar 

  • Garcia-Regalado A, Guzman-Hernandez ML, Ramirez-Rangel I, Robles-Molina E, Balla T, Vazquez-Prado J, Reyes-Cruz G (2008) G protein-coupled receptor-promoted trafficking of Gbeta1gamma2 leads to AKT activation at endosomes via a mechanism mediated by Gbeta1gamma2-Rab11a interaction. Mol Biol Cell 19(10):4188–4200. doi:10.1091/mbc.E07-10-1089, pii:E07-10-1089

    Article  PubMed  CAS  Google Scholar 

  • Gonzalo S, Linder ME (1998) SNAP-25 palmitoylation and plasma membrane targeting require a functional secretory pathway. Mol Biol Cell 9(3):585–597

    PubMed  CAS  Google Scholar 

  • Goodwin JS, Drake KR, Rogers C, Wright L, Lippincott-Schwartz J, Philips MR, Kenworthy AK (2005) Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway. J Cell Biol 170(2):261–272

    Article  PubMed  CAS  Google Scholar 

  • Gopalakrishna KN, Doddapuneni K, Boyd KK, Masuho I, Martemyanov KA, Artemyev NO (2011) Interaction of transducin with uncoordinated 119 protein (UNC119): implications for the model of transducin trafficking in rod photoreceptors. J Biol Chem 286(33):28954–28962. doi:10.1074/jbc.M111.268821, pii:M111.268821

    Article  PubMed  CAS  Google Scholar 

  • Gotta M, Ahringer J (2001) Distinct roles for Galpha and Gbetagamma in regulating spindle position and orientation in Caenorhabditis elegans embryos. Nat Cell Biol 3(3):297–300

    Article  PubMed  CAS  Google Scholar 

  • Gurdal H, Seasholtz TM, Wang HY, Brown RD, Johnson MD, Friedman E (1997) Role of G alpha q or G alpha o proteins in alpha 1-adrenoceptor subtype-mediated responses in Fischer 344 rat aorta. Mol Pharmacol 52(6):1064–1070

    PubMed  CAS  Google Scholar 

  • Hallak H, Brass LF, Manning DR (1994) Failure to myristoylate the alpha subunit of Gz is correlated with an inhibition of palmitoylation and membrane attachment, but has no affect on phosphorylation by protein kinase C. J Biol Chem 269(6):4571–4576

    PubMed  CAS  Google Scholar 

  • Hampoelz B, Hoeller O, Bowman SK, Dunican D, Knoblich JA (2005) Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins. Nat Cell Biol 7(11):1099–1105. doi:10.1038/ncb1318, pii:ncb1318

    Article  PubMed  CAS  Google Scholar 

  • Hancock JF, Paterson H, Marshall CJ (1990) A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell 63:133–139

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto Y, Matsuda T, Matsuura Y, Haga T, Fukada Y (2004) Production of N-lauroylated G protein alpha-subunit in Sf9 insect cells: the type of N-acyl group of Galpha influences G protein-mediated signal transduction. J Biochem 135(3):319–329

    Article  PubMed  CAS  Google Scholar 

  • Hepler JR, Kozasa T, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG (1993) Purification from Sf9 cells and characterization of recombinant Gq alpha and G11 alpha. Activation of purified phospholipase C isozymes by G alpha subunits. J Biol Chem 268(19):14367–14375

    PubMed  CAS  Google Scholar 

  • Hewavitharana T, Wedegaertner PB (2012) Non-canonical signaling and localizations of hetero­trimeric G proteins. Cell Signal 24(1):25–34. doi:10.1016/j.cellsig.2011.08.014, pii:S0898-6568(11)00260-9

    Article  PubMed  CAS  Google Scholar 

  • Hu LL, Wan SB, Niu S, Shi XH, Li HP, Cai YD, Chou KC (2011) Prediction and analysis of protein palmitoylation sites. Biochimie 93(3):489–496. doi:10.1016/j.biochi.2010.10.022, pii:S0300-9084(10)00383-4

    Article  PubMed  CAS  Google Scholar 

  • Hughes TE, Zhang H, Logothetis DE, Berlot CH (2001) Visualization of a functional Galpha q-green fluorescent protein fusion in living cells. Association with the plasma membrane is disrupted by mutational activation and by elimination of palmitoylation sites, but not be activation mediated by receptors or AlF4. J Biol Chem 276(6):4227–4235

    Article  PubMed  CAS  Google Scholar 

  • Humrich J, Bermel C, Grubel T, Quitterer U, Lohse MJ (2003) Regulation of phosducin-like protein by casein kinase 2 and N-terminal splicing. J Biol Chem 278(7):4474–4481. doi:10.1074/jbc.M206347200, pii:M206347200

    Article  PubMed  CAS  Google Scholar 

  • Humrich J, Bermel C, Bunemann M, Harmark L, Frost R, Quitterer U, Lohse MJ (2005) Phosducin-like protein regulates G-protein betagamma folding by interaction with tailless complex polypeptide-1alpha: dephosphorylation or splicing of PhLP turns the switch toward regulation of Gbetagamma folding. J Biol Chem 280(20):20042–20050

    Article  PubMed  CAS  Google Scholar 

  • Hynes TR, Mervine SM, Yost EA, Sabo JL, Berlot CH (2004) Live cell imaging of Gs and the beta2-adrenergic receptor demonstrates that both alphas and beta1gamma7 internalize upon stimulation and exhibit similar trafficking patterns that differ from that of the beta2-adrenergic receptor. J Biol Chem 279(42):44101–44112

    Article  PubMed  CAS  Google Scholar 

  • Iiri T, Backlund PS, Jones TL, Wedegaertner PB, Bourne HR (1996) Reciprocal regulation of Gs alpha by palmitate and the beta gamma subunit. Proc Natl Acad Sci USA 93(25):14592–14597

    Article  PubMed  CAS  Google Scholar 

  • Irannejad R, Wedegaertner PB (2010) Regulation of constitutive cargo transport from the trans-Golgi network to plasma membrane by Golgi-localized G protein betagamma subunits. J Biol Chem 285(42):32393–32404. doi:10.1074/jbc.M110.154963, pii:M110.154963

    Article  PubMed  CAS  Google Scholar 

  • Jamora C, Takizawa PA, Zaarour RF, Denesvre C, Faulkner DJ, Malhotra V (1997) Regulation of Golgi structure through heterotrimeric G proteins. Cell 91(5):617–626

    Article  PubMed  CAS  Google Scholar 

  • Jamora C, Yamanouye N, Van Lint J, Laudenslager J, Vandenheede JR, Faulkner DJ, Malhotra V (1999) Gbetagamma-mediated regulation of Golgi organization is through the direct activation of protein kinase D. Cell 98(1):59–68

    Article  PubMed  CAS  Google Scholar 

  • Johnson RS, Ohguro H, Palczewski K, Hurley JB, Walsh KA, Neubert TA (1994) Heterogeneous N-acylation is a tissue- and species-specific posttranslational modification. J Biol Chem 269:21067–21071

    PubMed  CAS  Google Scholar 

  • Jones TL, Simonds WF, Merendino JJ, Brann MR, Spiegel AM (1990) Myristoylation of an inhibitory GTP-binding protein alpha subunit is essential for its membrane attachment. Proc Natl Acad Sci USA 87(2):568–572

    Article  PubMed  CAS  Google Scholar 

  • Knol JC, Engel R, Blaauw M, Visser AJ, van Haastert PJ (2005) The phosducin-like protein PhLP1 is essential for G{beta}{gamma} dimer formation in Dictyostelium discoideum. Mol Cell Biol 25(18):8393–8400

    Article  PubMed  CAS  Google Scholar 

  • Kokame K, Fukada Y, Yoshizawa T, Takao T, Shimonishi Y (1992) Lipid modification at the N terminus of photoreceptor G-protein α-subunit. Nature 359:749–752

    Article  PubMed  CAS  Google Scholar 

  • Kosloff M, Elia N, Selinger Z (2002) Structural homology discloses a bifunctional structural motif at the N-termini of G alpha proteins. Biochemistry 41(49):14518–14523

    Article  PubMed  CAS  Google Scholar 

  • Kosloff M, Elia N, Joel-Almagor T, Timberg R, Zars TD, Hyde DR, Minke B, Selinger Z (2003) Regulation of light-dependent Gqalpha translocation and morphological changes in fly photoreceptors. EMBO J 22(3):459–468

    Article  PubMed  CAS  Google Scholar 

  • Kosloff M, Alexov E, Arshavsky VY, Honig B (2008) Electrostatic and lipid anchor contributions to the interaction of transducin with membranes: mechanistic implications for ­activation and translocation. J Biol Chem 283(45):31197–31207. doi:10.1074/jbc.M803799200, pii:M803799200

    Article  PubMed  CAS  Google Scholar 

  • Kubota S, Kubota H, Nagata K (2006) Cytosolic chaperonin protects folding intermediates of Gbeta from aggregation by recognizing hydrophobic beta-strands. Proc Natl Acad Sci USA 103(22):8360–8365. doi:10.1073/pnas.0600195103, pii:0600195103

    Article  PubMed  CAS  Google Scholar 

  • Lambert NA (2008) Dissociation of heterotrimeric g proteins in cells. Sci Signal 1(25):re5. doi:10.1126/scisignal.125re5, pii:scisignal.125re5

    Article  PubMed  Google Scholar 

  • Lane KT, Beese LS (2006) Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res 47(4):681–699. doi:10.1194/jlr.R600002-JLR200, pii:R600002-JLR200

    Article  PubMed  CAS  Google Scholar 

  • Levis MJ, Bourne HR (1992) Activation of the α subunit of Gs in intact cells alters its abundance, rate of degradation, and membrane avidity. J Cell Biol 119:1297–1307

    Article  PubMed  CAS  Google Scholar 

  • Li YX, Shao YH, Deng NY (2011) Improved prediction of palmitoylation sites using PWMs and SVM. Protein Pept Lett 18(2):186–193, pii:BSP/ PPL/ E pub/0239

    Article  PubMed  CAS  Google Scholar 

  • Lobo S, Greentree WK, Linder ME, Deschenes RJ (2002) Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J Biol Chem 277(43):41268–41273

    Article  PubMed  CAS  Google Scholar 

  • Loisel TP, Ansanay H, Adam L, Marullo S, Seifert R, Lagace M, Bouvier M (1999) Activation of the beta(2)-adrenergic receptor-Galpha(s) complex leads to rapid depalmitoylation and inhibition of repalmitoylation of both the receptor and Galpha(s). J Biol Chem 274(43):31014–31019

    Article  PubMed  CAS  Google Scholar 

  • Lukov GL, Hu T, McLaughlin JN, Hamm HE, Willardson BM (2005) Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly. EMBO J 24(11):1965–1975

    Article  PubMed  CAS  Google Scholar 

  • Lukov GL, Baker CM, Ludtke PJ, Hu T, Carter MD, Hackett RA, Thulin CD, Willardson BM (2006) Mechanism of assembly of G protein betagamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the cytosolic chaperonin complex. J Biol Chem 281(31):22261–22274. doi:10.1074/jbc.M601590200, pii:M601590200

    Article  PubMed  CAS  Google Scholar 

  • Marrari Y, Crouthamel M, Irannejad R, Wedegaertner PB (2007) Assembly and trafficking of heterotrimeric G proteins. Biochemistry 46(26):7665–7677

    Article  PubMed  CAS  Google Scholar 

  • Martin DD, Beauchamp E, Berthiaume LG (2011) Post-translational myristoylation: fat matters in cellular life and death. Biochimie 93(1):18–31. doi:10.1016/j.biochi.2010.10.018, pii:S0300-9084(10)00378-0

    Article  PubMed  CAS  Google Scholar 

  • Matsuda T, Takao T, Shimonishi Y, Murata M, Asano T, Yoshizawa T, Fukada Y (1994) Characterization of interactions between transducin α/βγ-subunits and lipid membranes. J Biol Chem 269(48):30358–30363

    PubMed  CAS  Google Scholar 

  • McLaughlin S, Aderem A (1995) The myristoyl-electrostatic switch: a modulator of reversible protein-membrane interactions. Trends Biochem Sci 20:272–280

    Article  PubMed  CAS  Google Scholar 

  • Michaelson D, Ahearn I, Bergo M, Young S, Philips M (2002) Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum and Golgi. Mol Biol Cell 13(9):3294–3302

    Article  PubMed  CAS  Google Scholar 

  • Miserey-Lenkei S, Lenkei Z, Parnot C, Corvol P, Clauser E (2001) A functional enhanced green fluorescent protein (EGFP)-tagged angiotensin II at(1a) receptor recruits the endogenous Galphaq/11 protein to the membrane and induces its specific internalization independently of receptor-g protein coupling in HEK-293 cells. Mol Endocrinol 15(2):294–307

    Article  PubMed  CAS  Google Scholar 

  • Morales J, Fishburn CS, Wilson PT, Bourne HR (1998) Plasma membrane localization of G alpha z requires two signals. Mol Biol Cell 9(1):1–14

    PubMed  CAS  Google Scholar 

  • Mumby SM, Heukeroth RO, Gordon JI, Gilman AG (1990) G-protein α-subunit expression, myristoylation, and membrane association in COS cells. Proc Natl Acad Sci USA 87(2):728–732

    Article  PubMed  CAS  Google Scholar 

  • Mumby SM, Kleuss C, Gilman AG (1994) Receptor regulation of G-protein palmitoylation. Proc Natl Acad Sci USA 91(7):2800–2804

    Article  PubMed  CAS  Google Scholar 

  • Murray D, McLaughlin S, Honig B (2001) The role of electrostatic interactions in the regulation of the membrane association of G protein beta gamma heterodimers. J Biol Chem 276(48):45153–45159

    Article  PubMed  CAS  Google Scholar 

  • Neubert TA, Johnson RS, Hurley JB, Walsh KA (1992) The rod transducin α subunit amino terminus is heterogeneously fatty acylated. J Biol Chem 267:18274–18277

    PubMed  CAS  Google Scholar 

  • Pedone KH, Hepler JR (2007) The importance of N-terminal polycysteine and polybasic sequences for G14alpha and G16alpha palmitoylation, plasma membrane localization, and signaling function. J Biol Chem 282(35):25199–25212

    Article  PubMed  CAS  Google Scholar 

  • Pesanova Z, Novotny J, Cerny J, Milligan G, Svoboda P (1999) Thyrotropin-releasing hormone-induced depletion of G(q)alpha/G(11)alpha proteins from detergent-insensitive membrane domains. FEBS Lett 464(1–2):35–40, pii:S001457939901666X

    Article  PubMed  CAS  Google Scholar 

  • Peterson JJ, Orisme W, Fellows J, McDowell JH, Shelamer CL, Dugger DR, Smith WC (2005) A role for cytoskeletal elements in the light-driven translocation of proteins in rod photoreceptors. Invest Ophthalmol Vis Sci 46(11):3988–3998. doi:10.1167/iovs.05-0567, pii:46/11/3988

    Article  PubMed  Google Scholar 

  • Preininger AM, Hamm HE (2004) G protein signaling: insights from new structures. Sci STKE 2004(218):re3. doi:10.1126/stke.2182004re3, pii:stke.2182004re3

    Article  PubMed  Google Scholar 

  • Ransnäs LA, Svoboda P, Jasper JR, Insel PA (1989) Stimulation of β-adrenergic receptors of S49 lymphoma cells redistributes the α subunit of the stimulatory G protein between cytosol and membranes. Proc Natl Acad Sci USA 86:7900–7903

    Article  PubMed  Google Scholar 

  • Ren J, Wen L, Gao X, Jin C, Xue Y, Yao X (2008) CSS-Palm 2.0: an updated software for palmitoylation sites prediction. Protein Eng Des Sel 21(11):639–644. doi:10.1093/protein/gzn039, pii:gzn039

    Article  PubMed  CAS  Google Scholar 

  • Resh MD (1999) Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1451(1):1–16

    Article  PubMed  CAS  Google Scholar 

  • Resh MD (2006) Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol 2(11):584–590

    Article  PubMed  CAS  Google Scholar 

  • Rocks O, Peyker A, Kahms M, Verveer PJ, Koerner C, Lumbierres M, Kuhlmann J, Waldmann H, Wittinghofer A, Bastiaens PI (2005) An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science 307(5716):1746–1752

    Article  PubMed  CAS  Google Scholar 

  • Rocks O, Gerauer M, Vartak N, Koch S, Huang ZP, Pechlivanis M, Kuhlmann J, Brunsveld L, Chandra A, Ellinger B, Waldmann H, Bastiaens PI (2010) The palmitoylation machinery is a spatially organizing system for peripheral membrane proteins. Cell 141(3):458–471. doi:10.1016/j.cell.2010.04.007, pii:S0092-8674(10)00381-8

    Article  PubMed  CAS  Google Scholar 

  • Roth AF, Feng Y, Chen L, Davis NG (2002) The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J Cell Biol 159(1):23–28

    Article  PubMed  CAS  Google Scholar 

  • Saini DK, Kalyanaraman V, Chisari M, Gautam N (2007) A family of G protein betagamma subunits translocate reversibly from the plasma membrane to endomembranes on receptor activation. J Biol Chem 282(33):24099–24108

    Article  PubMed  CAS  Google Scholar 

  • Saini DK, Chisari M, Gautam N (2009) Shuttling and translocation of heterotrimeric G proteins and Ras. Trends Pharmacol Sci 30(6):278–286. doi:10.1016/j.tips.2009.04.001, pii:S0165-6147(09)00056-X

    Article  PubMed  CAS  Google Scholar 

  • Saini DK, Karunarathne WK, Angaswamy N, Saini D, Cho JH, Kalyanaraman V, Gautam N (2010) Regulation of Golgi structure and secretion by receptor-induced G protein betagamma complex translocation. Proc Natl Acad Sci USA 107(25):11417–11422. doi:10.1073/pnas.1003042107, pii:1003042107

    Article  PubMed  CAS  Google Scholar 

  • Scarselli M, Donaldson JG (2009) Constitutive internalization of G protein-coupled receptors and G proteins via clathrin-independent endocytosis. J Biol Chem 284(6):3577–3585. doi:10.1074/jbc.M806819200, pii:M806819200

    Article  PubMed  CAS  Google Scholar 

  • Seitz HR, Heck M, Hofmann KP, Alt T, Pellaud J, Seelig A (1999) Molecular determinants of the reversible membrane anchorage of the G-protein transducin. Biochemistry 38(25):7950–7960. doi:10.1021/bi990298+, pii:bi990298+

    Article  PubMed  CAS  Google Scholar 

  • Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF, Busch CJ, Kane C, Hubel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg ME, Draguhn A, Rehmsmeier M, Martinez J, Schratt GM (2009) A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol 11(6):705–716. doi:10.1038/ncb1876, pii:ncb1876

    Article  PubMed  CAS  Google Scholar 

  • Slepak VZ, Hurley JB (2008) Mechanism of light-induced translocation of arrestin and transducin in photoreceptors: interaction-restricted diffusion. IUBMB Life 60(1):2–9. doi:10.1002/iub.7

    Article  PubMed  CAS  Google Scholar 

  • Sokolov M, Lyubarsky AL, Strissel KJ, Savchenko AB, Govardovskii VI, Pugh EN Jr, Arshavsky VY (2002) Massive light-driven translocation of transducin between the two major compartments of rod cells: a novel mechanism of light adaptation. Neuron 34(1):95–106, pii:S0896627302006360

    Article  PubMed  CAS  Google Scholar 

  • Sokolov M, Strissel KJ, Leskov IB, Michaud NA, Govardovskii VI, Arshavsky VY (2004) Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse. J Biol Chem 279(18):19149–19156. doi:10.1074/jbc.M311058200, pii:M311058200

    Article  PubMed  CAS  Google Scholar 

  • Sondek J, Siderovski DP (2001) Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta-propeller scaffolding. Biochem Pharmacol 61(11):1329–1337

    Article  PubMed  CAS  Google Scholar 

  • Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB (1996) Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature 379(6563):369–374. doi:10.1038/379369a0

    Article  PubMed  CAS  Google Scholar 

  • Song J, Hirschman J, Gunn K, Dohlman HG (1996) Regulation of membrane and subunit interactions by N-myristoylation of a G protein α subunit in yeast. J Biol Chem 271(34):20273–20283

    Article  PubMed  CAS  Google Scholar 

  • Stanislaus D, Janovick JA, Brothers S, Conn PM (1997) Regulation of G(q/11)alpha by the gonadotropin-releasing hormone receptor. Mol Endocrinol 11(6):738–746

    Article  PubMed  CAS  Google Scholar 

  • Stanislaus D, Ponder S, Ji TH, Conn PM (1998) Gonadotropin-releasing hormone receptor couples to multiple G proteins in rat gonadotrophs and in GGH3 cells: evidence from palmitoylation and overexpression of G proteins. Biol Reprod 59(3):579–586

    Article  PubMed  CAS  Google Scholar 

  • Stevens PA, Pediani J, Carrillo JJ, Milligan G (2001) Coordinated agonist regulation of receptor and G protein palmitoylation and functional rescue of palmitoylation-deficient mutants of the G protein G11alpha following fusion to the alpha1b-adrenoreceptor: palmitoylation of G11alpha is not required for interaction with beta*gamma complex. J Biol Chem 276(38):35883–35890

    Article  PubMed  CAS  Google Scholar 

  • Takida S, Wedegaertner PB (2003) Heterotrimer formation, together with isoprenylation, is required for plasma membrane targeting of Gbeta gamma. J Biol Chem 278(19):17284–17290

    Article  PubMed  CAS  Google Scholar 

  • Takida S, Wedegaertner PB (2004) Exocytic pathway-independent plasma membrane targeting of heterotrimeric G proteins. FEBS Lett 567(2–3):209–213

    Article  PubMed  CAS  Google Scholar 

  • Tall GG, Krumins AM, Gilman AG (2003) Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem 278(10):8356–8362. doi:10.1074/jbc.M211862200, pii:M211862200

    Article  PubMed  CAS  Google Scholar 

  • Thiyagarajan MM, Bigras E, Van Tol HH, Hebert TE, Evanko DS, Wedegaertner PB (2002) Activation-induced subcellular redistribution of G alpha(s) is dependent upon its unique N-terminus. Biochemistry 41(30):9470–9484

    Article  PubMed  CAS  Google Scholar 

  • Thomas CJ, Briknarova K, Hilmer JK, Movahed N, Bothner B, Sumida JP, Tall GG, Sprang SR (2011) The nucleotide exchange factor Ric-8A is a chaperone for the conformationally dynamic nucleotide-free state of Galphai1. PLoS One 6(8):e23197. doi:10.1371/journal.pone.0023197, pii:PONE-D-11-08669

    Article  PubMed  CAS  Google Scholar 

  • Tsutsumi R, Fukata Y, Noritake J, Iwanaga T, Perez F, Fukata M (2009) Identification of G protein alpha subunit-palmitoylating enzyme. Mol Cell Biol 29(2):435–447. doi:10.1128/MCB.01144-08, pii:MCB.01144-08

    Article  PubMed  CAS  Google Scholar 

  • Van Dyke RW (2004) Heterotrimeric G protein subunits are located on rat liver endosomes. BMC Physiol 4:1. doi:10.1186/1472-6793-4-1, pii:1472-6793-4-1

    Article  PubMed  Google Scholar 

  • Wan M, Li J, Herbst K, Zhang J, Yu B, Wu X, Qiu T, Lei W, Lindvall C, Williams BO, Ma H, Zhang F, Cao X (2011) LRP6 mediates cAMP generation by G protein-coupled receptors through regulating the membrane targeting of Galpha(s). Sci Signal 4(164):ra15. doi:10.1126/scisignal.2001464, pii:4/164/ra15

    Article  PubMed  Google Scholar 

  • Wang H, Ng KH, Qian H, Siderovski DP, Chia W, Yu F (2005) Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Nat Cell Biol 7(11):1091–1098. doi:10.1038/ncb1317, pii:ncb1317

    Article  PubMed  CAS  Google Scholar 

  • Wedegaertner PB, Bourne HR (1994) Activation and depalmitoylation of Gs alpha. Cell 77(7):1063–1070

    Article  PubMed  CAS  Google Scholar 

  • Wedegaertner PB, Chu DH, Wilson PT, Levis MJ, Bourne HR (1993) Palmitoylation is required for signaling functions and membrane attachment of Gq alpha and Gs alpha. J Biol Chem 268(33):25001–25008

    PubMed  CAS  Google Scholar 

  • Wedegaertner PB, Bourne HR, von Zastrow M (1996) Activation-induced subcellular redistribution of Gsa. Mol Biol Cell 7(8):1225–1233

    PubMed  CAS  Google Scholar 

  • Wells CA, Dingus J, Hildebrandt JD (2006) Role of the chaperonin CCT/TRiC complex in G protein betagamma-dimer assembly. J Biol Chem 281(29):20221–20232. doi:10.1074/jbc.M602409200, pii:M602409200

    Article  PubMed  CAS  Google Scholar 

  • Willardson BM, Howlett AC (2007) Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding. Cell Signal 19(12):2417–2427. doi:10.1016/j.cellsig.2007.06.013, pii:S0898-6568(07)00190-8

    Article  PubMed  CAS  Google Scholar 

  • Wilson PT, Bourne HR (1995) Fatty acylation of alpha z. Effects of palmitoylation and myristoylation on alpha z signaling. J Biol Chem 270(16):9667–9675

    Article  PubMed  CAS  Google Scholar 

  • Wise A, Parenti M, Milligan G (1997) Interaction of the G-protein G11alpha with receptors and phosphoinositidase C: the contribution of G-protein palmitoylation and membrane association. FEBS Lett 407(3):257–260

    Article  PubMed  CAS  Google Scholar 

  • Wright LP, Philips MR (2006) Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J Lipid Res 47(5):883–891

    Article  PubMed  CAS  Google Scholar 

  • Yu JZ, Rasenick MM (2002) Real-time visualization of a fluorescent G(alpha)(s): dissociation of the activated G protein from plasma membrane. Mol Pharmacol 61(2):352–359

    Article  PubMed  CAS  Google Scholar 

  • Zeidman R, Jackson CS, Magee AI (2009) Protein acyl thioesterases (review). Mol Membr Biol 26(1):32–41. doi:10.1080/09687680802629329, pii:907244142

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W (2011) UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci 14(7):874–880. doi:10.1038/nn.2835, pii:nn.2835

    Article  PubMed  CAS  Google Scholar 

  • Zheng B, Lavoie C, Tang TD, Ma P, Meerloo T, Beas A, Farquhar MG (2004) Regulation of ­epidermal growth factor receptor degradation by heterotrimeric Galphas protein. Mol Biol Cell 15(12):5538–5550. doi:10.1091/mbc.E04-06-0446, pii:E04-06-0446

    Article  PubMed  CAS  Google Scholar 

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Wedegaertner, P.B. (2012). G Protein Trafficking. In: Dupré, D., Hébert, T., Jockers, R. (eds) GPCR Signalling Complexes – Synthesis, Assembly, Trafficking and Specificity. Subcellular Biochemistry, vol 63. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4765-4_11

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