Skip to main content

Synthesis and Assembly of G Protein βγ Dimers: Comparison of In Vitro and In Vivo Studies

  • Chapter
  • First Online:

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

Abstract

The heterotrimeric GTP-binding proteins (G proteins) are the canonical cellular machinery used with the approximately 700 G protein-coupled receptors (GPCRs) in the human genome to transduce extracellular signals across the plasma membrane. The synthesis of the constituent G protein subunits, and their assembly into Gβγ dimers and G protein heterotrimers, determines the signaling repertoire for G-protein/GPCR signaling in cells. These synthesis/assembly ­processes are intimately related to two other overlapping events in the intricate pathway leading to formation of G protein signaling complexes, posttranslational modification and intracellular trafficking of G proteins. The assembly of the Gβγ dimer is a complex process involving multiple accessory proteins and organelles. The mechanisms involved are becoming increasingly appreciated, but are still incompletely understood. In vitro and in vivo (cellular) studies provide different perspectives of these processes, and a comparison of them can provide insight into both our current level of understanding and directions to be taken in future investigations.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Barral JM, Broadley SA, Schaffar G, Hartl FU (2004) Roles of molecular chaperones in protein misfolding diseases. Semin Cell Dev Biol 15(1):17–29. doi:10.1016/j.semcdb.2003.12.010

    Article  PubMed  CAS  Google Scholar 

  • Bayewitch ML, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds WF, Vogel Z (1998) Inhibition of adenylyl cyclase isoforms V and VI by various Gßγ subunits. FASEB J 12:1019–1025

    PubMed  CAS  Google Scholar 

  • Bermak JC, Li M, Bullock C, Zhou QY (2001) Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein. Nat Cell Biol 3(5):492–498. doi:10.1038/35074561

    Article  PubMed  CAS  Google Scholar 

  • Birnbaumer L (1990) G proteins in signal transduction. Annu Rev Pharmacol Toxicol 30:675–705

    Article  PubMed  CAS  Google Scholar 

  • Blaauw M, Knol JC, Kortholt A, Roelofs J, Ruchira PM, Visser AJWG, van Haastert PJM (2003) Phosducin-like proteins in dictyostelium discoideum: implications for the phosducin family of proteins. EMBO J 22:5047–5057

    Article  PubMed  CAS  Google Scholar 

  • Bourne HR, Sanders DA, McCormick F (1990) The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125–132

    Article  PubMed  CAS  Google Scholar 

  • Brackley KI, Grantham J (2009) Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation. Cell Stress Chaperones 14(1):23–31. doi:10.1007/s12192-008-0057-x

    Article  PubMed  CAS  Google Scholar 

  • Cabrera-Vera TM, VanHauwe J, Thomas TO, Medkova M, Prieninger A, Mazzoni MR, Hamm HE (2003) Insights into G protein structure, function, and regulation. Endocr Rev 24:765–781

    Article  PubMed  CAS  Google Scholar 

  • Cook LA, Schey KL, Wilcox MD, Dingus J, Ettling R, Nelson T, Knapp DR, Hildebrandt JD (2006) Proteomic analysis of bovine brain G protein gamma subunit processing heterogeneity. Mol Cell Proteomics 5:671–685

    PubMed  CAS  Google Scholar 

  • Craig E (2003) Eukaryotic chaperonins: lubricating the folding of WD-repeat proteins. Curr Biol 13:R904–R905

    Article  PubMed  CAS  Google Scholar 

  • Craig E, Huang P, Aron R, Andrew A (2006) The diverse roles of J-proteins, the obligate Hsp70 co-chaperone. Rev Physiol Biochem Pharmacol 156:1–21

    Article  PubMed  CAS  Google Scholar 

  • Dietrich A, Meister M, Spicher K, Schultz G, Camps M, Gierschik P (1992) Expression, characteization and purification of soluble G protein beta/gamma dimers composed of defined subunits in baculovirus infected cells. FEBS Lett 313:220–224

    Article  PubMed  CAS  Google Scholar 

  • Dingus J, Wells CA, Campbell L, Cleator JH, Robinson K, Hildebrandt JD (2005) G protein betagamma dimer formation: Gbeta and Ggamma differentially determine efficiency of in vitro dimer formation. Biochemistry 44:11882–11890

    Article  PubMed  CAS  Google Scholar 

  • Downes GB, Gautam N (1999) The G protein subunit gene families. Genomics 62:544–552

    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

    Article  PubMed  CAS  Google Scholar 

  • Etchells SA, Meyer AS, Yam AY, Roobol A, Miao Y, Shao Y, Carden MJ, Skach WR, Frydman J, Johnson AE (2005) The cotranslational contacts between ribosome-bound nascent polypeptides and the subunits of the hetero-oligomeric chaperonin TRiC probed by photocross-linking. J Biol Chem 280(30):28118–28126. doi:10.1074/jbc.M504110200

    Article  PubMed  CAS  Google Scholar 

  • Evanko DS, Thiyagarajan MM, Siderovski DP, Wedegaertner DP (2001) Gbetagamma isoforms selectively rescue plasma membrane localization and palmitoylation of mutant galphas and galphaq. J Biol Chem 276:23945–23953

    Article  PubMed  CAS  Google Scholar 

  • Farr GW, Scharl EC, Schumacher RJ, Sondek S, Howrwich AL (1997) Chaperonin-mediated folding in the eukaryotic ytosol proceeds through rounds of release of native and nonnative forms. Cell 89:927–937

    Article  PubMed  CAS  Google Scholar 

  • Feldman DE, Thulasiraman V, Ferreyra RG, Frydman J (1999) Formation of the VHL-elngin BC tumor suppressor complex is mediated by the chaperonin TRiC. Mol Cell 4:1051–1061

    Article  PubMed  CAS  Google Scholar 

  • Fletcher JE, Lindorfer MA, DeFilippo JM, Yasuda H, Guilmard M, Garrison JC (1998) The G protein b5 subunit interacts selectively with the Gq alpha subunit. J Biol Chem 273:636–644

    Article  PubMed  CAS  Google Scholar 

  • Ford CE, Skiba NP, Bae H, Daaka Y, Reuveny E, Shekter LR, Rosal R, Weng G, Yang C-S, Iyengar R, Miller RJ, Jan LY, Lefkowitz RJ, Hamm HE (1998) Molecular basis for interactions of G protein beta-gamma subunits with effectors. Science 280:1271–1274

    Article  PubMed  CAS  Google Scholar 

  • Fu H-W, Casey P (1999) Enzymology and biology of CaaX protein prenylation. Recent Prog Horm Res 54:315–343

    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 4:1–13

    Article  CAS  Google Scholar 

  • Garcia-Higuera I, Fenoglio J, Li Y, Lewis C, Panchenko MP, Reiner O, Smith TF, Neer EJ (1996a) Folding of proteins with WD-repeats: comparison of six members of the WD-repeat superfamily to the G protein beta subunit. Biochemistry 35(44):13985–13994. doi:10.1021/bi9612879

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Higuera I, Thomas TC, Yi F, Neer EJ (1996b) Intersubunit surfaces in G protein alpha/beta/gamma heterotrimers. Analysis by cross linking and mutagenesis of beta/gamma. J Biol Chem 271:528–535

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Higuera I, Gaitatzes C, Smith T, Neer EJ (1998) Folding a WD repeat propeller. Role of highly conserved aspartic acid residues in the G protein beta subunit and Sec13. J Biol Chem 273:9041–9049

    Article  PubMed  CAS  Google Scholar 

  • Garritsen A, Simonds WF (1994) Multiple domains of G protein beta confer subunit specificity in bg interactions. J Biol Chem 269:24418–24423

    PubMed  CAS  Google Scholar 

  • Gaudet R, Bohm A, Sigler PB (1996) Crystal structure at 2.4 A resolution of the complex of transducin beta/gamma and its regulator, phosducin. Cell 87:577–588

    Article  PubMed  CAS  Google Scholar 

  • Gilman AG (1987) G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56:615–649

    Article  PubMed  CAS  Google Scholar 

  • Graber SG, Figler RA, Garrison JC (1992a) Expression and purification of functional G protein alpha subunits using a baculovirus expression system. J Biol Chem 267:1271–1278

    PubMed  CAS  Google Scholar 

  • Graber SG, Figler RA, Kalman-Maltese VK, Robishaw JD, Garrison JC (1992b) Expression of functional G protein beta/gamma dimers of defined subunit composition using a baculovirus expression system. J Biol Chem 267:13123–13126

    PubMed  CAS  Google Scholar 

  • Gross M, Olin A, Hessefort S, Bender S (1993) Control of protein synthesis by hemin. Purification of a rabbit reticulocyte hsp 70 and characterization of its regulation of the activation of the hemin-controlled eIF-2(a) kinase. J Biol Chem 269:22738–22748

    Google Scholar 

  • Hamm HE (1998) The many faces of G protein signaling. J Biol Chem 273:669–672

    Article  PubMed  CAS  Google Scholar 

  • Hawes RE, van Biesen T, Koch WJ, Luttrell LM, Lefkowitz RJ (1995) Distinct pathways of Gi- and Gq-mediated mitogen-activated protein kinase activation. J Biol Chem 270:17148–17153

    Article  PubMed  CAS  Google Scholar 

  • Higgins JB, Casey PJ (1994) In vitro processing of recombinant G protein gamma subunits. Requirements for assembly of an active beta/gamma complex. J Biol Chem 269:9067–9073

    PubMed  CAS  Google Scholar 

  • Higgins JB, Casey PJ (1996) The role of prenylation in G protein assembly and function. Cell Signal 8:433–437

    Article  PubMed  CAS  Google Scholar 

  • Hildebrandt JD (1997) Role of subunit diversity in signaling by heterotrimeric G proteins. Biochem Pharmacol 54:325–339

    Article  PubMed  CAS  Google Scholar 

  • Hildebrandt JD (2011) Heterogeneous prenyl processing of the heterotrimeric G protein gamma subunits. The Enzym Prot Prenylation Part A 29:97–124

    Article  CAS  Google Scholar 

  • Hildebrandt JD, Codina J, Risinger R, Birnbaumer L (1984) Identification of a gamma subunit associated with the adenylyl cyclase regulatory proteins Ns and Ni. J Biol Chem 259:2039–2042

    PubMed  CAS  Google Scholar 

  • Howlett AC, Gray AJ, Hunter JM, Willardson BM (2009) Role of molecular chaperones in g protein beta 5/regulator of G protein signaling dimer assembly and G protein beta gamma dimer specificity. J Biol Chem. doi:10.1074/jbc.M900800200, pii:M900800200

  • 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 278:4474–4481

    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 folding by interaction with tailless complex polypeptide-1 alpha. Dephosphorylation or splicing of phlp turns the switch toward regulation of G folding. J Biol Chem 280:20042–20050

    Article  PubMed  CAS  Google Scholar 

  • Hynes TR, Tang L, Mervine SM, Sabo JL, Yost EA, Devreotes PN, Berlot CH (2004) Visualization of G protein betagamma dimers using bimolecular fluorescence complementation demonstrates roles for both beta and gamma in subcellular targeting. J Biol Chem 279:30279–30286

    Article  PubMed  CAS  Google Scholar 

  • Iniguez-Lluhi JA, Simon MI, Robishaw JD, Gilman AG (1992) G protein beta/gamma subunits synthesized in sf9 cells. Functional characterization and the significance of prenylation of gamma. J Biol Chem 267:23409–23417

    PubMed  CAS  Google Scholar 

  • Jewett AI, Shea JE (2010) Reconciling theories of chaperonin accelerated folding with experimental evidence. Cell Mol Life Sci 67(2):255–276

    Article  PubMed  CAS  Google Scholar 

  • Jones MB, Garrison JC (1999) Instability of the G protein beta5 subunit in detergent. Anal Biochem 268:126–133

    Article  PubMed  CAS  Google Scholar 

  • Jones MB, Siderovski DP, Hooks SB (2004) The gbetagamma dimer as a novel source of selectivity in G-protein signaling: GGL-ing at convention. Mol Interv 4:200–214

    Article  PubMed  CAS  Google Scholar 

  • Kilpatrick EL, Hildebrandt JD (2007) Sequence dependence and differential expression of Gγ5 subunit isoforms of the heterotrimeric G proteins variably processed after prenylation in mammalian cells. J Biol Chem 282:14038–14047

    Article  PubMed  CAS  Google Scholar 

  • Kleuss C, Krause E (2003) Galpha(s) is palmitoylated at the N-terminal glycine. EMBO J 22:826–832

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kubota S, Kubota H, Nagata K (2006) Cytosolic chaperonin protects folding intermediates of G beta from aggregation by recognizing hydrophobic beta strands. Proc Natl Acad Sci U S A 103:8360–8365

    Article  PubMed  CAS  Google Scholar 

  • Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB (1996) The 2.0 Angstrom crystal structure of a heterotrimeric G protein. Nature 379:311–319

    Article  PubMed  CAS  Google Scholar 

  • Lee C, Murakami T, Simonds WF (1995) Identification of a discrete region of the G protein gamma subunit conferring selectivity in beta/gamma complex formation. J Biol Chem 270:8779–8784

    Article  PubMed  CAS  Google Scholar 

  • Li X, Hummer A, Han J, Xie M, Melnik-Martinez K, Moreno RL, Buck M, Mark MD, Herlitz S (2006) G protein beta2 subunit-derived peptides for inhibition and induction of G protein pathways. Examination of voltage-gated calcium and G protein inwardly rectyfying potasium channels. J Biol Chem 280:23945–23959

    Article  CAS  Google Scholar 

  • Lindorfer MA, Myung CS, Savino Y, Yasuda H, Khazan R, Garrison JC (1998) Differential activity of the G protein beta-5 gamma-2 subunit at receptors and effectors. J Biol Chem 273:34429–34436

    Article  PubMed  CAS  Google Scholar 

  • Loew A, Ho Y, Blundell T, Bax B (1998) Phosducin induces a structural change in transducin betagamma. Structure 8:1007–1019

    Google Scholar 

  • Lukov GL, Myung CS, McIntire WE, Shao J, Zimmerman SS, Garrison JC, Willardson BM (2004) Role of the isoprenyl pocket of the G protein beta gamma subunit complex in the binding of phosducin and phosducin-like protein. Biochemistry 43(19):5651–5660. doi:10.1021/bi035903u

    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 24:1965–1975

    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

    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. doi:10.1021/bi700338m

    Article  PubMed  CAS  Google Scholar 

  • Martin-Benito J, Bertrand S, Hu T, Ludtke PJ, McLaughlin JN, Willardson BM, Carrascosa JL, Valpuesta JM (2004) Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein. Proc Natl Acad Sci U S A 101:17410–17415

    Article  PubMed  CAS  Google Scholar 

  • McCallum CD, Do H, Johnson AE, Frydman J (2000) The interaction of the chaperonin tailless complex polypeptide 1 (TCP1) ring complex (TRiC) with ribosome-bound nascent chains examined using photo-cross-linking. J Cell Biol 149(3):591–602

    Article  PubMed  CAS  Google Scholar 

  • McIntire WE, MacCleery G, Garrison JC (2001) The G protein beta subunit is a determinant in the coupling of Gs to the beta-1 adrenergic and A2a adenosine receptors. J Biol Chem 276:15801–15809

    Article  PubMed  CAS  Google Scholar 

  • McIntire WE, MacCleery G, Murphree LJ, Kerchner KR, Linden J, Garrison JC (2006) Influence of differential stability of G protein dimers containing the 11 subunit on functional activity at the M1 muscarinic receptor, A1 adenosine receptor, and phospholipase C. Biochemistry 45:11616–11631

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin JN, Thulin CD, Hart SJ, Resing KA, Ahn NG, Willardson BM (2002) Regulatory interaction of phosducin-like protein with the cytosolic chaperonin complex. Proc Natl Acad Sci U S A 99:7962–7967

    Article  PubMed  CAS  Google Scholar 

  • Mende U, Schmidt CJ, Yi F, Spring DJ, Neer EJ (1995) The G protein gamma subunit. Requirements for dimerization with beta subunits. J Biol Chem 270:15892–15898

    Article  PubMed  CAS  Google Scholar 

  • Mervine SM, Yost EA, Sabo JL, Hynes TR, Berlot CH (2006) Analysis of G protein betagamma dimer formation in live cells using multicolor bimolecular fluorescence complementation demonstrates preferences of beta1 for particular gamma subunits. Mol Pharmacol 70:194–205

    PubMed  CAS  Google Scholar 

  • Meyer AS, Gillespie JR, Walther D, Millet IA, Doniach S, Frydman J (2003) Closing the folding chamber of the eukaryotic chaperonin requires the transition state of ATP hydrolysis. Cell 113(3):369–381

    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 13:3294–3302

    Article  PubMed  CAS  Google Scholar 

  • Mumby SM, Casey PJ, Gilman AG, Gutowski S, Sternweis PC (1990) G protein gamma subunits contain a 20-carbon isoprenoid. Proc Natl Acad Sci U S A 87:5873–5877

    Article  PubMed  CAS  Google Scholar 

  • Muntz KH, Sternweis PC, Gilman AG, Mumby SM (1993) Influence of gamma subunit prenylation on association of guanine nucleotide binding regulatory proteins with membranes. Mol Biol Cell 3:49–61

    Google Scholar 

  • Ong O, Yamane HK, Phan KB, Fong HKW, Bok D, Lee RH, Fung BK (1995) Molecular cloning and characterization of the G protein gamma subunit of cone photoreceptors. J Biol Chem 270:8495–8500

    Article  PubMed  CAS  Google Scholar 

  • Petersen TM, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8:785–786

    Article  PubMed  CAS  Google Scholar 

  • Poon LS, Chan AS, Wong YH (2009) Gbeta3 Forms distinct dimers with specific Ggamma subunits and preferentially activates the beta3 isoform of phospholipase C. Cell Signal 21(5):737–744. doi:10.1016/j.cellsig.2009.01.018, pii:S0898-6568(09)00017-5

    Article  PubMed  CAS  Google Scholar 

  • Pronin AN, Gautam N (1992) Interaction between G protein beta and gamma subunit types is selective. Proc Natl Acad Sci U S A 89:6220–6224

    Article  PubMed  CAS  Google Scholar 

  • Ray K, Kunsch C, Bonner LM, Robishaw JD (1995) Isolation of cDNA clones encoding eight different human G protein gamma subunits, including three novel forms designated the gamma-4, gamma-10 and gamma-11 subunits. J Biol Chem 270:21765–21771

    Article  PubMed  CAS  Google Scholar 

  • Rehm A, Ploegh HL (1997) Assembly and intracellular targeting of the beta-gamma subunits of heterotrimer G proteins. J Cell Biol 137:305–317

    Article  PubMed  CAS  Google Scholar 

  • Richardson M, Robishaw JD (1999) The alpha 2A-adrenergic receptor discriminates between Gi heterotrimers of different beta gamma subunit composition in Sf9 insect cell membranes. J Biol Chem 274:13525–13533

    Article  PubMed  CAS  Google Scholar 

  • Riggs DL, Cox MB, Cheung-Flynn J, Prapapanich V, Carrigan PE, Smith DF (2004) Functional specificity of co-chaperone interactions with Hsp90 client proteins. Crit Rev Biochem Mol Biol 39:279–295

    Article  PubMed  CAS  Google Scholar 

  • Robishaw JD, Kalman VK, Proulx KL (1992) Production, processing and partial purification of functional G protein beta/gamma subunits in baculovirus infected insect cells. Biochem J 286:677–680

    PubMed  CAS  Google Scholar 

  • Rosskopf D, Koch K, Habick C, Geerder J, Ludwig A, Wwilhelms S, Jakobs KH, Sifffert W (2003a) Interaction of Gbeta3s, a splice variant of the G-protein Gbeta3, with ggamma- and galpha-proteins. Cell Signal 5648:1–10

    Google Scholar 

  • Rosskopf D, Nikula C, Manthey I, Joisten M, Frey U, Kohnen S, Siffert W (2003b) The human G protein beta4 subunit: gene structure, expression, Ggamma and effector interaction. FEBS Lett 544:27–32

    Article  PubMed  CAS  Google Scholar 

  • Saibil HR (2008) Chaperone machines in action. Curr Opin Struct Biol 18(1):35–42. doi:10.1016/j.sbi.2007.11.006

    Article  PubMed  CAS  Google Scholar 

  • Schaber MD, O’Hara MB, Garsky VM, Mosser SC, Bergstrom JD, Moores SL, Marshall MS, Friedman PA, Dixon RA, Gibbs JB (1990) Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase. J Biol Chem 265(25):14701–14704

    PubMed  CAS  Google Scholar 

  • Schmidt CJ, Neer EJ (1991) In vitro synthesis of G protein beta/gamma dimers. J Biol Chem 266:4538–4544

    PubMed  CAS  Google Scholar 

  • Schmidt CJ, Thomas TC, Levine MA, Neer EJ (1992) Specificity of G protein beta and gamma subunit interactions. J Biol Chem 267:13807–13810

    PubMed  CAS  Google Scholar 

  • Schroder S, Lohse MJ (1996) Inhibition of G protein beta/gamma subunit function by phosducin-like protein. Proc Natl Acad Sci U S A 93:2100–2104

    Article  PubMed  CAS  Google Scholar 

  • Schwindinger WF, Robishaw JD (2001) Heterotrimeric G-protein betagamma dimers in growth and differentiation. Oncogene 20:1653–1660

    Article  PubMed  CAS  Google Scholar 

  • Seabra MC, Goldstein JL, Sudhof TC, Brown MS (1992) Rab geranylgeranyl transferase. J Biol Chem 267:14497–14503

    PubMed  CAS  Google Scholar 

  • Siegers K, Bolter B, Schwarz JP, Bottcher UMK, Guha S, Hartl FU (2003) Tric/CCT cooperates with different upstream chaperones in the folding of distinct perotein classes. EMBO J 22:5230–5240

    Article  PubMed  CAS  Google Scholar 

  • Simonds WF, Butrynski JE, Gautam N, Unson CG, Spiegel AM (1991) G protein beta/gamma dimers. Membrane targeting requires subunit coexpression and intact gamma C-a-a-X domain. J Biol Chem 266:5363–5366

    PubMed  CAS  Google Scholar 

  • Simons CT, Staes A, Rommelaere H, Ampe C, Lewis SA, Cowan NJ (2004) Selective contribution of eukaryotic prefoldin subunits to actin and tubulin binding. J Biol Chem 279:4196–4203

    Article  PubMed  CAS  Google Scholar 

  • Smith T (2008) Diversity of WD-repeat proteins. Subcell Biochem Coronin Fam Protein 48:20–30

    Article  Google Scholar 

  • Smotrys JE, Linder ME (2004) Palmitoylation of intracellular signaling proteins: regulation and function. Annu Rev Biochem 73:559–587

    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 2.1 Angstrom resolution. Nature 379:369–374

    Article  PubMed  CAS  Google Scholar 

  • Spiess C, Meyer AS, Reissmann S, Frydman J (2004) Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets. Trends Cell Biol 14(11):598–604. doi:10.1016/j.tcb.2004.09.015

    Article  PubMed  CAS  Google Scholar 

  • Stirnimann CU, Petsalaki E, Russell RB, Muller CW (2010) WD40 Proteins propel cellular networks. Trends Biochem Sci 35:65–574

    Article  CAS  Google Scholar 

  • Takida S, Wedegaertner DP (2004) Exocytic pathway-independent plasma membrane targeting of heterotrimeric G proteins. FEBS Lett 567:2009–2213

    Article  CAS  Google Scholar 

  • Thibault C, Sganga MW, MIles MF (1997) Interaction of phosducin-like protein with G protein betagamma subunits. J Biol Chem 272:12253–12256

    Article  PubMed  CAS  Google Scholar 

  • Ueda N, Iniguez-Lluhi JA, Lee E, Smrcka AV, Robishaw JD, Gilman AG (1994) G protein beta/gamma subunits. Simplified purification and properties of novel isoforms. J Biol Chem 269:4388–4395

    PubMed  CAS  Google Scholar 

  • Valpuesta JM, Martin-Benito J, Gomez-Puertas P, Carrascosa JL, Willison KR (2002) Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett 529:11–16

    Article  PubMed  CAS  Google Scholar 

  • Vane JR, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120

    Article  PubMed  CAS  Google Scholar 

  • Wall MA, Coleman DE, Lee E, Iniguez-Lluhi JA, Posner BA, Gilman AG, Sprang SR (1995) The structure of the G protein heterotrimer G alpha-i1 beta-1 gamma-2. Cell 83:1047–1058

    Article  PubMed  CAS  Google Scholar 

  • Wall MA, Posner BA, Sprang SR (1998) Structural basis of activity and subunit recognition in G protein heterotrimers. Structure 6:1169–1183

    Article  PubMed  CAS  Google Scholar 

  • Watson AJ, Katz A, Simon MI (1994) A fifth member of the mammalian G-protein beta subunit family. J Biol Chem 269:22150–22156

    PubMed  CAS  Google Scholar 

  • Watson AJ, Aragay AM, Slepak VZ, Simon MI (1996) A novel form of the G protein beta subunit G beta-5 is specifically expressed in the vertebrate retina. J Biol Chem 271:28154–28160

    Article  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 281:20221–20232

    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

    Article  PubMed  CAS  Google Scholar 

  • Winter-Vann AM, Casey PJ (2005) Post-prenylation-processing enzymes as new targets in oncogenesis. Nat Rev Cancer 5:407–412

    Article  CAS  Google Scholar 

  • Witherow DS, Wang Q, Levay K, Cabera JL, Chen J, Willars GB, Slepak VZ (2000) Complexes of the G protein gbeta 5 with the regulators of G protein signaling RGS7 and RGS9. J Biol Chem 275:24872–24880

    Article  PubMed  CAS  Google Scholar 

  • Wolfe JT, Wang H, Howard J, Garrison JC, Barrett PQ (2003) T-type calcium channel regulation by specific G-protein bold betabig gamma subunits. Nature 424:209–213

    Article  PubMed  CAS  Google Scholar 

  • Yan K, Kalyanaraman V, Gautam N (1996) Differential ability to form the G protein beta/gamma complex among members of the beta and gamma subunit families. J Biol Chem 271:7141–7146

    Article  PubMed  CAS  Google Scholar 

  • Yost EA, Mervine SM, Sabo JL, Hynes TR, Berlot CH (2007) Live cell analysis of G protein beta5 complex formation, function, and targeting. Mol Pharmacol 72:812–825

    Article  PubMed  CAS  Google Scholar 

  • Zhang S, Coso OA, Lee C, Gutkind S, Simonds WF (1996) Selective activation of effector pathways by brain specific G protein beta-5. J Biol Chem 271:33575–33579

    Article  PubMed  CAS  Google Scholar 

  • Zhou JY, Siderovski DP, Miller RJ (2000) Selective regulation of N-type Ca channels by different combinations of G-protein beta/gamma subunits and RGS proteins. J Neurosci 20:7143–7148

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John D. Hildebrandt .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Dingus, J., Hildebrandt, J.D. (2012). Synthesis and Assembly of G Protein βγ Dimers: Comparison of In Vitro and In Vivo Studies. 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_9

Download citation

Publish with us

Policies and ethics