Les protéines G : les transducteurs privilégiés des récepteurs à sept domaines transmembranaires.

G protein; G protein-coupled receptors; GPCR; RCPG; Récepteurs couplés aux protéines G; biased signaling; intracellular signaling; protéines G; signalisation biaisée; signalisation intracellulaire; Receptors, G-Protein-Coupled; GTP-Binding Proteins; Humans; Signal Transduction/physiology; Transducers; GTP-Binding Proteins/metabolism; Receptors, G-Protein-Coupled/metabolism; Signal Transduction; Biochemistry, Genetics and Molecular Biology (all)

Abstract :

[en] G protein-coupled receptors or GPCR are the most abundant membrane receptors in our genome with around 800 members. They play an essential role in most physiological and pathophysiological phenomena. In addition, they constitute 30% of the targets of currently marketed drugs and remain an important reservoir for new innovative therapies. Their main effectors are heterotrimeric G proteins. These are composed of 3 subunits, α, β and γ, which, upon coupling with a GPCR, dissociate into Gα and Gβγ to activate numerous signaling pathways. This article describes some of the recent advances in understanding the function and role of heterotrimeric G proteins. After a short introduction to GPCRs, the history of the discovery of G proteins is briefly described. Then, the fundamental mechanisms of activation, signaling and regulation of G proteins are reviewed. New paradigms concerning intracellular signaling, specific recognition of G proteins by GPCRs as well as biased signaling are also discussed.
[fr] [fr] TITLE: Les protéines G : les transducteurs privilégiés des récepteurs à sept domaines transmembranaires. ABSTRACT: Les récepteurs couplés aux protéines G ou RCPG sont les récepteurs membranaires les plus abondants de notre génome avec environ 800 membres. Ils jouent un rôle essentiel dans la plupart des phénomènes physiologiques et physiopathologiques. De plus, ils constituent 30 % des cibles de médicaments actuellement commercialisés et restent un réservoir important pour de nouvelles thérapies innovantes. Leurs principaux effecteurs sont les protéines G hétérotrimériques. Celles-ci sont composées de 3 sous-unités, α, β et γ qui, lors du couplage avec un RCPG, se dissocient en Gα et Gβγ pour activer de nombreuses voies de signalisation. Cet article décrit certaines des avancées récentes dans la compréhension du fonctionnement et du rôle des protéines G hétérotrimériques. Après une courte introduction sur les RCPG, l’historique de la découverte des protéines G est décrit succinctement. Ensuite, les mécanismes fondamentaux de l’activation, la signalisation et la régulation des protéines G sont passés en revue. Les nouveaux paradigmes qui concernent la signalisation intracellulaire, la reconnaissance spécifique des protéines G par les RCPG ainsi que la signalisation biaisée sont également abordés.

Disciplines :

Pharmacy, pharmacology & toxicology
Biochemistry, biophysics & molecular biology

Author, co-author :

Hanson, Julien ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique

Language :

French

Title :

Les protéines G : les transducteurs privilégiés des récepteurs à sept domaines transmembranaires.

Alternative titles :

[en] G proteins: privileged transducers of 7-transmembrane spanning receptors.

Publication date :

2021

Journal title :

Biologie Aujourd'hui

ISSN :

2105-0678

eISSN :

2105-0686

Publisher :

EDP Sciences, France

Volume :

215

Issue :

3-4

Pages :

95 - 106

Peer reviewed :

Editorial reviewed

Additional URL :

https://www.biologie-journal.org/10.1051/jbio/2021011/pdf

Available on ORBi :

since 26 August 2024

Statistics

Number of views

4 (0 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Abboud, D., Daly, A.F., Dupuis, N., Bahri, M.A., Inoue, A., Chevigné, A., Ectors, F., Plenevaux, A., Pirotte, B., Beckers, A. Hanson, J. (2020). GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11. Nat Commun, 11, 4752.
Alexander, S.P., Christopoulos, A., Davenport, A.P., Kelly, E., Mathie, A., Peters, J.A., Veale, E.L., Armstrong, J.F., Faccenda, E., Harding, S.D., Pawson, A.J., Southan, C., Davies, J.A., Abbracchio, M.P., Alexander, W., Al-Hosaini, K., Bäck, M., Barnes, N.M., Bathgate, R., Beaulieu, J.-M., Bernstein, K.E., Bettler, B., Birdsall, N.J.M., Blaho, V., Boulay, F., Bousquet, C., Bräuner-Osborne, H., Burnstock, G., Calé, G., Castaño, J.P., Catt, K.J., Ceruti, S., Chazot, P., Chiang, N., Chini, B., Chun, J., Cianciulli, A., Civelli, O., Clapp, L.H., Couture, R., Csaba, Z., Dahlgren, C., Dent, G., Singh, K.D., Douglas, S.D., Dournaud, P., Eguchi, S., Escher, E., Filardo, E.J., Fong, T., Fumagalli, M., Gainetdinov, R.R., Gasparo, M. de, Gerard, C., Gershengorn, M., Gobeil, F., Goodfriend, T.L., Goudet, C., Gregory, K.J., Gundlach, A.L., Hamann, J., Hanson, J., Hauger, R.L., Hay, D.L., Heinemann, A., Hollenberg, M.D., Holliday, N.D., Horiuchi, M., Hoyer, D., Hunyady, L., Husain, A., Ijzerman, A.P., Inagami, T., Jacobson, K.A., Jensen, R.T., Jockers, R., Jonnalagadda, D., Karnik, S., Kaupmann, K., Kemp, J., Kennedy, C., Kihara, Y., Kitazawa, T., Kozielewicz, P., Kreienkamp, H.-J., Kukkonen, J.P., Langenhan, T., Leach, K., Lecca, D., Lee, J.D., Leeman, S.E., Leprince, J., Li, X.X., Williams, T.L., Lolait, S.J., Lupp, A., Macrae, R., Maguire, J., Mazella, J., McArdle, C.A., Melmed, S., Michel, M.C., Miller, L.J., Mitolo, V., Mouillac, B., Müller, C.E., Murphy, P., Nahon, J.-L., Ngo, T., Norel, X., Nyimanu, D., OaCarroll, A.-M., Offermanns, S., Panaro, M.A., Parmentier, M., Pertwee, R.G., Pin, J.-P., Prossnitz, E.R., Quinn, M., Ramachandran, R., Ray, M., Reinscheid, R.K., Rondard, P., Rovati, G.E., Ruzza, C., Sanger, G.J., Schöneberg, T., Schulte, G., Schulz, S., Segaloff, D.L., Serhan, C.N., Stoddart, L.A., Sugimoto, Y., Summers, R., Tan, V.P., Thal, D., Thomas, W.W., Timmermans, P.B.M.W.M., Tirupula, K., Tulipano, G., Unal, H., Unger, T., Valant, C., Vanderheyden, P., Vaudry, D., Vaudry, H., Vilardaga, J.-P., Walker, C.S., Wang, J.M., Ward, D.T., Wester, H.-J., Willars, G.B., Woodruff, T.M., Yao, C., Ye, R.D. (2021). The Concise Guide to Pharmacology 2021/22: G protein-coupled receptors. Br J Pharmacol, 178 (Suppl 1), S27-S156.
Almutairi, F., Lee, J.-K. Rada, B. (2020). Regulator of G protein signaling 10: Structure, expression and functions in cellular physiology and diseases. Cell Signal, 75, 109765.
Al-Sabah, S., Al-Fulaij, M., Shaaban, G., Ahmed, H.A., Mann, R.J., Donnelly, D., Bünemann, M. Krasel, C. (2014). The GIP receptor displays higher basal activity than the GLP-1 receptor but does not recruit GRK2 or arrestin3 effectively. PLoS One, 9 (9), e106890.
Arang, N., Gutkind, J.S. (2020). G protein-coupled receptors and heterotrimeric G proteins as cancer drivers. FEBS Lett, 594, 4201-4232.
Avasarala, S., Bikkavilli, R.K., Van Scoyk, M., Zhang, W., Lapite, A., Hostetter, L., Byers, J.T., Heasley, L.E., Sohn, J.W., Winn, R.A. (2013). Heterotrimeric G-protein, Gα16, is a critical downstream effector of non-canonical Wnt signaling and a potent inhibitor of transformed cell growth in non small cell lung cancer. PLoS One, 8 (10), e76895.
Bourne, H.R., Coffino, P., Tomkins, G.M. (1975). Selection of a variant lymphoma cell deficient in adenylate cyclase. Science, 187, 750-752.
Calebiro, D., Koszegi, Z. (2019). The subcellular dynamics of GPCR signaling. Mol Cell Endocrinol, 483, 24-30.
Calebiro, D., Nikolaev, V.O., Gagliani, M.C., de Filippis, T., Dees, C., Tacchetti, C., Persani, L., Lohse, M.J. (2009). Persistent CAMP-signals triggered by internalized G-proteinacoupled receptors. PLoS Biol, 7 (8), e1000172.
Calebiro, D., Nikolaev, V.O., Persani, L., Lohse, M.J. (2010). Signaling by internalized G-protein-coupled receptors. Trends Pharmacol Sci, 31, 221-228.
Cao, W., Luttrell, L.M., Medvedev, A.V., Pierce, K.L., Daniel, K.W., Dixon, T.M., Lefkowitz, R.J., Collins, S. (2000). Direct binding of activated C-Src to the I? 3-adrenergic receptor is required for MAP kinase activation. J Biol Chem, 275, 38131-38134.
Carpenter, B., Tate, C.G. (2017). Active state structures of G protein-coupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces. Curr Opin Struct Biol, 45, 124-132.
Coffino, P., Bourne, H.R., Tomkins, G.M. (1975). Somatic genetic analysis of cyclic AMP action: Selection of unresponsive mutants. J Cell Physiol, 85, 603-610.
Conklin, B.R., Farfel, Z., Lustig, K.D., Julius, D., Bourne, H.R. (1993). Substitution of three amino acids switches receptor specificity of Gq alpha to that of Gi alpha. Nature, 363, 274-276.
Cordeaux, Y., Nickolls, S.A., Flood, L.A., Graber, S.G., Strange, P.G. (2001). Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtype. J Biol Chem, 276, 28667-28675.
Davenport, A.P., Harmar, A.J. (2013). Evolving pharmacology of orphan GPCRs: IUPHAR commentary. Br J Pharmacol, 170, 693-695.
De Lean, A., Stadel, J.M., Lefkowitz, R.J. (1980). A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J Biol Chem, 255, 7108-7117.
DeGraff, J.L., Gagnon, A.W., Benovic, J.L., Orsini, M.J. (1999). Role of arrestins in endocytosis and signaling of α2-adrenergic receptor subtypes. J Biol Chem, 274, 11253-11259.
DeVree, B.T., Mahoney, J.P., Vélez-Ruiz, G.A., Rasmussen, S.G.F., Kuszak, A.J., Edwald, E., Fung, J.-J., Manglik, A., Masureel, M., Du, Y., Matt, R.A., Pardon, E., Steyaert, J., Kobilka, B.K., Sunahara, R.K. (2016). Allosteric coupling from G protein to the agonist-binding pocket in GPCRs. Nature, 535, 182-186.
Doi, M., Murai, I., Kunisue, S., Setsu, G., Uchio, N., Tanaka, R., Kobayashi, S., Shimatani, H., Hayashi, H., Chao, H.-W., Nakagawa, Y., Takahashi, Y., Hotta, Y., Yasunaga, J.-I., Matsuoka, M., Hastings, M.H., Kiyonari, H., Okamura, H. (2016). Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour. Nat Commun, 7, 10583.
Dorsam, R.T., Gutkind, J.S. (2007). G-protein-coupled receptors and cancer. Nat Rev Cancer, 7, 79-94.
Doyen, P.J., Beckers, P., Brook, G.A., Hermans, E. (2020). Regulators of G protein signalling as pharmacological targets for the treatment of neuropathic pain. Pharmacol Res, 160, 105148.
Dror, R.O., Mildorf, T.J., Hilger, D., Manglik, A., Borhani, D.W., Arlow, D.H., Philippsen, A., Villanueva, N., Yang, Z., Lerch, M.T., Hubbell, W.L., Kobilka, B.K., Sunahara, R.K., Shaw, D.E. (2015). Signal transduction. Structural basis for nucleotide exchange in heterotrimeric G proteins. Science, 348, 1361-1365.
Duc, N.M., Kim, H.R., Chung, K.Y. (2017). Recent progress in understanding the conformational mechanism of heterotrimeric G protein activation. Biomol Ther, 25, 4-11.
Dupuis, N., Laschet, C., Franssen, D., Szpakowska, M., Gilissen, J., Geubelle, P., Soni, A., Parent, A.-S., Pirotte, B., Chevigné, A., Twizere, J.-C., Hanson, J. (2017). Activation of the orphan G protein-coupled receptor GPR27 by surrogate ligands promotes β-arrestin 2 recruitment. Mol Pharmacol, 91, 595-608.
Feinstein, T.N., Yui, N., Webber, M.J., Wehbi, V.L., Stevenson, H.P., King, J.D. Jr, Hallows, K.R., Brown, D., Bouley, R., Vilardaga, J.-P. (2013). Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin. J Biol Chem, 288, 27849-27860.
Ferrandon, S., Feinstein, T.N., Castro, M., Wang, B., Bouley, R., Potts, J.T., Gardella, T.J., Vilardaga, J.-P. (2009). Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat Chem Biol, 5, 734-742.
Fields, T.A., Casey, P.J. (1997). Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. Biochem J, 321, 561-571.
Flegel, C., Manteniotis, S., Osthold, S., Hatt, H., Gisselmann, G. (2013). Expression profile of ectopic olfactory receptors determined by deep sequencing. PLoS One, 8, e55368.
Flock, T., Ravarani, C.N.J., Sun, D., Venkatakrishnan, A.J., Kayikci, M., Tate, C.G., Veprintsev, D.B., Babu, M.M. (2015). Universal allosteric mechanism for Gα activation by GPCRs. Nature, 524, 173-179.
Flock, T., Hauser, A.S., Lund, N., Gloriam, D.E., Balaji, S., Babu, M.M. (2017). Selectivity determinants of GPCR-G-protein binding. Nature, 545, 317-322.
Fong, H.K., Yoshimoto, K.K., Eversole-Cire, P., Simon, M.I. (1988). Identification of a GTP-binding protein alpha subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Proc Natl Acad Sci USA, 85, 3066-3070.
Fredriksson, R., Lagerström, M.C., Lundin, L.-G., Schiöth, H.B. (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol, 63, 1256-1272.
García-Nafría, J., Tate, C.G. (2019). Cryo-EM structures of GPCRs coupled to Gs, Gi and Go. Mol Cell Endocrinol, 488, 1-13.
Gazi, L., Nickolls, S.A.: Strange, P.G. (2003). Functional coupling of the human dopamine D2 receptor with G alpha I1, G alpha I2, G alpha I3 and G alpha o G proteins: Evidence for agonist regulation of G protein selectivity. Br J Pharmacol, 138, 775-786.
Gilman, A.G. (2012). Silver spoons and other personal reflections. Annu Rev Pharmacol Toxicol, 52, 1-19.
Grundmann, M., Merten, N., Malfacini, D., Inoue, A., Preis, P., Simon, K., Rüttiger, N., Ziegler, N., Benkel, T., Schmitt, N.K., Ishida, S., Müller, I., Reher, R., Kawakami, K., Inoue, A., Rick, U., Kühl, T., Imhof, D., Aoki, J., König, G.M., Hoffmann, C., Gomeza, J., Wess, J. Kostenis, E. (2018). Lack of beta-arrestin signaling in the absence of active G proteins. Nat Commun, 9 (341), 1-16.
Hanyaloglu, A.C., von Zastrow, M. (2008). Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu Rev Pharmacol Toxicol, 48, 537-568.
Hauser, A.S., Attwood, M.M., Rask-Andersen, M., Schiöth, H.B., Gloriam, D.E. (2017). Trends in GPCR drug discovery: New agents, targets and indications. Nat Rev Drug Discov, 16, 829-842.
Hauser, A.S., Avet, C., Normand, C., Manchini, A., Inoue, A., Bouvier, M., Gloriam, D. (2021). GPCR-G Protein Selectivity aa Unified Meta-Analysis. https://doi.org/10.1101/2021.09.07.459250.
Hebert-Chatelain, E., Desprez, T., Serrat, R., Bellochio, L., Grandes, P., Benard, G., Marsicano, G. (2016). A cannabinoid link between mitochondria and memory. Biochim Biophys Acta Bioenerg, 1857, e118.
Hepler, J.R., Gilman, A.G. (1992). G proteins. Trends Biochem Sci, 17, 383-387.
Hermans, E. (2003). Biochemical and pharmacological control of the multiplicity of coupling at G-protein-coupled receptors. Pharmacol Ther, 99, 25-44.
Hislop, J.N., Caunt, C.J., Sedgley, K.R., Kelly, E., Mundell, S., Green, L.D. McArdle, C.A. (2005). Internalization of gonadotropin-releasing hormone receptors (GnRHRs): Does arrestin binding to the C-terminal tail target GnRHRs for dynamin-dependent internalization? J Mol Endocrinol, 35, 177-189.
Hollinger, S., Hepler, J.R. (2002). Cellular regulation of RGS proteins: Modulators and integrators of G protein signaling. Pharmacol Rev, 54, 527-559.
Iiri, T., Herzmark, P., Nakamoto, J.M., van Dop, C., Bourne, H.R. (1994). Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function. Nature, 371, 164-168.
Inoue, A., Raimondi, F., Kadji, F.M.N., Singh, G., Kishi, T., Uwamizu, A., Ono, Y., Shinjo, Y., Ishida, S., Arang, N., Kawakami, K., Gutkind, J.S., Aoki, J., Russell, R.B. (2019). Illuminating G-protein-coupling selectivity of GPCRs. Cell, 177, 1933-1947.
Irannejad, R., Tomshine, J.C., Tomshine, J.R., Chevalier, M., Mahoney, J.P., Steyaert, J., Rasmussen, S.G.F., Sunahara, R.K., El-Samad, H., Huang, B., von Zastrow, M. (2013). Conformational biosensors reveal GPCR signalling from endosomes. Nature, 495, 534-538.
Irannejad, R., von Zastrow, M. (2014). GPCR signaling along the endocytic pathway. Curr Opin Cell Biol, 27, 109-116.
Ismail, S., Gherardi, M.-J., Froese, A., Zanoun, M., Gigoux, V., Clerc, P., Gaits-Iacovoni, F., Steyaert, J., Nikolaev, V.O., Fourmy, D. (2016). Internalized receptor for glucose-dependent insulinotropic peptide stimulates adenylyl cyclase on early endosomes. Biochem Pharmacol, 120, 33-45.
Karamitri, A., Plouffe, B., Bonnefond, A., Chen, M., Gallion, J., Guillaume, J.-L., Hegron, A., Boissel, M., Canouil, M., Langenberg, C., Wareham, N.J., Le Gouill, C., Lukasheva, V., Lichtarge, O., Froguel, P., Bouvier, M., Jockers, R. (2018). Type 2 diabetes-associated variants of the MT2 melatonin receptor affect distinct modes of signaling. Sci Signal, 11 (eaan6622), 1-14.
Katritch, V., Cherezov, V., Stevens, R.C. (2013). Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol, 53, 531-556.
Kenakin, T. (2011). Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther, 336, 296-302.
Kenakin, T. (2013). New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2. Br J Pharmacol, 168, 554-575.
Kimple, M.E., Joseph, J.W., Bailey, C.L., Fueger, P.T., Hendry, I.A., Newgard, C.B., Casey, P.J. (2008). Gαz negatively regulates insulin secretion and glucose clearance. J Biol Chem, 283, 4560-4567.
Knight, K.M., Ghosh, S., Campbell, S.L., Lefevre, T.J., Olsen, R.H.J., Smrcka, A.V., Valentin, N.H., Yin, G., Vaidehi, N., Dohlman, H.G. (2021). A universal allosteric mechanism for G protein activation. Mol Cell, 81, 1384-1396.
Kolb, P., Kenakin, T., Alexander, S., Bermudez, M., Bohn, L., Breinholt, C., Bouvier, M., Ehlert, F., Hill, S.J., Martemyanov, K., Neubig, R., Onaran, O.H., Rajagopal, S., Roth, B.L., Selent, J., Shukla, A.K., Sommer, M.E., Gloriam, D.E. (2021). International Union of Basic and Clinical Pharmacology. Recommendations for GPCR ligand bias. Authorea, September. https://doi.org/10.22541/au.163129851.17708337/v1.
Kostenis, E., Waelbroeck, M., Milligan, G. (2005). Techniques: Promiscuous Gα proteins in basic research and drug discovery. Trends Pharmacol Sci, 26, 595-602.
Kostenis, E., Pfeil, E.M., Annala, S. (2020). Heterotrimeric Gq proteins as therapeutic targets? J Biol Chem, 295, 5206-5215.
Kotowski, S.J., Hopf, F.W., Seif, T., Bonci, A., von Zastrow, M. (2011). Endocytosis promotes rapid dopaminergic signaling. Neuron, 71, 278-290.
Kuna, R.S., Girada, S.B., Asalla, S., Vallentyne, J., Maddika, S., Patterson, J.T., Smiley, D.L., DiMarchi, R.D., Mitra, P. (2013). Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic β-cells. Am J Physiol Endocrinol Metab, 305, E161-E170.
Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., Funke, R., Gage, D., Harris, K., Heaford, A., Howland, J., Kann, L., Lehoczky, J., LeVine, R., McEwan, P., McKernan, K., Meldrim, J., Mesirov, J.P., Miranda, C., Morris, W., Naylor, J., Raymond, C., Rosetti, M., Santos, R., Sheridan, A., Sougnez, C., Stange-Thomann, Y., Stojanovic, N., Subramanian, A., Wyman, D., Rogers, J., Sulston, J., Ainscough, R., Beck, S., Bentley, D., Burton, J., Clee, C., Carter, N., Coulson, A., Deadman, R., Deloukas, P., Dunham, A., Dunham, I., Durbin, R., French, L., Grafham, D., Gregory, S., Hubbard, T., Humphray, S., Hunt, A., Jones, M., Lloyd, C., McMurray, A., Matthews, L., Mercer, S., Milne, S., Mullikin, J.C., Mungall, A., Plumb, R., Ross, M., Shownkeen, R., Sims, S., Waterston, R.H., Wilson, R.K., Hillier, L.W., McPherson, J.D., Marra, M.A., Mardis, E.R., Fulton, L.A., Chinwalla, A.T., Pepin, K.H., Gish, W.R., Chissoe, S.L., Wendl, M.C., Delehaunty, K.D., Miner, T.L., Delehaunty, A., Kramer, J.B., Cook, L.L., Fulton, R.S., Johnson, D.L., Minx, P.J., Clifton, S.W., Hawkins, T., Branscomb, E., Predki, P., Richardson, P., Wenning, S., Slezak, T., Doggett, N., Cheng, J.F., Olsen, A., Lucas, S., Elkin, C., Uberbacher, E., Frazier, M., Gibbs, R.A., Muzny, D.M., Scherer, S.E., Bouck, J.B., Sodergren, E.J., Worley, K.C., Rives, C.M., Gorrell, J.H., Metzker, M.L., Naylor, S.L., Kucherlapati, R.S., Nelson, D.L., Weinstock, G.M., Sakaki, Y., Fujiyama, A., Hattori, M., Yada, T., Toyoda, A., Itoh, T., Kawagoe, C., Watanabe, H., Totoki, Y., Taylor, T., Weissenbach, J., Heilig, R., Saurin, W., Artiguenave, F., Brottier, P., Bruls, T., Pelletier, E., Robert, C., Wincker, P., Smith, D.R., Doucette-Stamm, L., Rubenfield, M., Weinstock, K., Lee, H.M., Dubois, J., Rosenthal, A., Platzer, M., Nyakatura, G., Taudien, S., Rump, A., Yang, H., Yu J., Wang J., Huang, G., Gu, J., Hood, L., Rowen, L., Madan, A., Qin, S., Davis, R.W., Federspiel, N.A., Abola, A.P., Proctor, M.J., Myers, R.M., Schmutz, J., Dickson, M., Grimwood, J., Cox, D.R., Olson, M.V., Kaul, R., Raymond, C., Shimizu, N., Kawasaki, K., Minoshima, S., Evans, G.A., Athanasiou, M., Schultz, R., Roe, B.A., Chen, F., Pan, H., Ramser, J., Lehrach, H., Reinhardt, R., McCombie, W.R., de la Bastide, M., Dedhia, N., Blöcker, H., Hornischer, K., Nordsiek, G., Agarwala, R., Aravind, L., Bailey, J.A., Bateman, A., Batzoglou, S., Birney, E., Bork, P., Brown, D.G., Burge, C.B., Cerutti, L., Chen, H.C., Church, D., Clamp, M., Copley, R.R., Doerks, T., Eddy, S.R., Eichler, E.E., Furey, T.S., Galagan, J., Gilbert, J.G., Harmon, C., Hayashizaki, Y., Haussler, D., Hermjakob, H., Hokamp, K., Jang, W., Johnson, L.S., Jones, T.A., Kasif, S., Kaspryzk, A., Kennedy, S., Kent, W.J., Kitts, P., Koonin, E.V., Korf, I., Kulp, D., Lancet, D., Lowe, T.M., McLysaght, A., Mikkelsen, T., Moran, J.V., Mulder, N., Pollara, V.J., Ponting, C.P., Schuler, G., Schultz, J., Slater, G., Smit, A.F., Stupka, E., Szustakowki, J., Thierry-Mieg, D., Thierry-Mieg, J., Wagner, L., Wallis, J., Wheeler, R., Williams, A., Wolf, Y.I., Wolfe, K.H., Yang, S.P., Yeh, R.F., Collins, F., Guyer, M.S., Peterson, J., Felsenfeld, A., Wetterstrand, K.A., Patrinos, A., Morgan, M.J., de Jong, P., Catanese, J.J., Osoegawa, K., Shizuya, H., Choi, S., Chen, Y.J., Szustakowki, J., International Human Genome Sequencing Consortium. (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860-921.
Laschet, C., Dupuis, N., Hanson, J. (2018). The G protein-coupled receptors deorphanization landscape. Biochem Pharmacol, 153, 62-74.
Laschet, C., Dupuis, N., Hanson, J. (2019). A dynamic and screening-compatible nanoluciferase-based complementation assay enables profiling of individual GPCR-G protein interactions. J Biol Chem, 294, 4079-4090.
Laschet, C., Hanson, J. (2021). Nanoluciferase-based complementation assay to detect GPCR-G protein interaction. Methods Mol Biol, 2268, 149-157.
Le Mercier, A., Bonnavion, R., Yu, W., Alnouri, M.W., Ramas, S., Zhang, Y., Jäger, Y., Roquid, K.A., Jeong, H.-W., Sivaraj, K.K., Cho, H., Chen, X., Strilic, B., Sijmonsma, T., Adams, R., Schroeder, T., Rieger, M.A., Offermanns, S. (2021). GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis. Proc Natl Acad Sci USA, 118 (e2021596118), 1-10.
Lefkowitz, R.J. (2018). A serendipitous scientist. Annu Rev Pharmacol Toxicol, 58, 17-32.
Li, J., Ge, Y., Huang, J.-X., Strømgaard, K., Zhang, X., Xiong, X.-F. (2020). Heterotrimeric G proteins as therapeutic targets in drug discovery. J Med Chem, 63, 5013-5030.
Lohse, M.J., Calebiro, D. (2013). Cell biology: Receptor signals come in waves. Nature, 495, 457-458.
Lohse, M.J., Hofmann, K.P. (2015). Spatial and temporal aspects of signaling by G-protein-coupled receptors. Mol Pharmacol, 88, 572-578.
Lyga, S., Volpe, S., Werthmann, R.C., Götz, K., Sungkaworn, T., Lohse, M.J., Calebiro, D. (2016). Persistent CAMP signaling by internalized LH receptors in ovarian follicles. Endocrinology, 157, 1613-1621.
Magalhaes, A.C., Dunn, H. Ferguson, S.S. (2012). Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins. Br J Pharmacol, 165, 1717-1736.
Mahoney, J.P., Sunahara, R.K. (2016). Mechanistic insights into GPCR-G protein interactions. Curr Opin Struct Biol, 41, 247-254.
Mancini, A., Avet, C., Breton, B., Le Gouill, C., Hauser, A., Normand, C., Gross, F., Lukasheva, V., Hogue, M., Morissette, S., Fauman, E., Fortin, J., Schann, S., Leroy, X., Gloriam, D., Bouvier, M. (2021). Use of novel EbBRET biosensors for comprehensive signaling profiling of one hundred therapeutically relevant human GPCRs. FASEB J, 35 (S1). https://doi.org/10.1096/fasebj.2021.35.s1.01694.
Marshall, F.H., Jones, K.A., Kaupmann, K., Bettler, B. (1999). GABABreceptors athe first 7TM heterodimers. Trends Pharmacol Sci, 20, 396-399.
Martemyanov, K.A. (2021). Mechanisms of Gβγ release upon GPCR activation. Trends Biochem Sci, 46, 703-704.
Masuho, I., Balaji, S., Muntean, B.S., Skamangas, N.K., Chavali, S., Tesmer, J.J.G., Babu, M.M., Martemyanov, K.A. (2020). A global map of G protein signaling regulation by RGS proteins. Cell, 183, 503-521.
Masuho, I., Skamangas, N.K., Muntean, B.S., Martemyanov, K.A. (2021). Diversity of the Gβγ complexes defines spatial and temporal bias of GPCR signaling. Cell Syst, 12, 324-337.
McKee, E.E., Bentley, A.T., Smith, R.M. Jr, Ciaccio, C.E. (1999). Origin of guanine nucleotides in isolated heart mitochondria. Biochem Biophys Res Commun, 257, 466-472.
McLaughlin, J.N., Shen, L., Holinstat, M., Brooks, J.D., Dibenedetto, E., Hamm, H.E. (2005). Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. J Biol Chem, 280, 25048-25059.
Milligan, G. Kostenis, E. (2006). Heterotrimeric G-proteins: A short history. Br J Pharmacol, 147, Suppl 1, S46-S55.
Milligan, G., Ward, R.J., Marsango, S. (2019). GPCR homo-oligomerization. Curr Opin Cell Biol, 57, 40-47.
Moreira, I.S. (2014). Structural features of the G-protein/GPCR interactions. Biochim Biophys Acta, 1840, 16-33.
Mukhopadhyay, S., Howlett, A.C. (2005). Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions. Mol Pharmacol, 67, 2016-2024.
Muntean, B.S., Masuho, I., Dao, M., Sutton, L.P., Zucca, S., Iwamoto, H., Patil, D.N., Wang, D., Birnbaumer, L., Blakely, R.D., Grill, B., Martemyanov, K.A. (2021). Gαo is a major determinant of cAMP signaling in the pathophysiology of movement disorders. Cell Rep, 34, 1-18.
Northup, J.K., Sternweis, P.C., Smigel, M.D., Schleifer, L.S., Ross, E.M., Gilman, A.G. (1980). Purification of the regulatory component of adenylate cyclase. Proc Natl Acad Sci USA, 77, 6516-6520.
OaHayre, M., Eichel, K., Avino, S., Zhao, X., Steffen, D.J., Feng, X., Kawakami, K., Aoki, J., Messer, K., Sunahara, R., Inoue, A., von Zastrow, M., Gutkind, J.S. (2017). Genetic evidence that β-arrestins are dispensable for the initiation of β2-adrenergic receptor signaling to ERK. Sci Signal, 10 (eaal3395), 1-13.
Okashah, N., Wan, Q., Ghosh, S., Sandhu, M., Inoue, A., Vaidehi, N., Lambert, N.A. (2019). Variable G protein determinants of GPCR coupling selectivity. Proc Natl Acad Sci USA, 116, 12054-12059.
Okinaga, S., Slattery, D., Humbles, A., Zsengeller, Z., Morteau, O., Kinrade, M.B., Brodbeck, R.M., Krause, J.E., Choe, H.-R., Gerard, N.P. Gerard, C. (2003). C5L2: A nonsignaling C5A binding protein. Biochemistry, 42, 9406-9415.
Oldham, W.M., Van Eps, N., Preininger, A.M., Hubbell, W.L., Hamm, H.E. (2006). Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Mol Biol, 13, 772-777.
Oldham, W.M., Hamm, H.E. (2007). How do receptors activate G proteins? Adv Protein Chem, 74, 67-93.
Oldham, W.M., Hamm, H.E. (2008). Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol, 9, 60-71.
Pandey, S., Kumari, P., Baidya, M., Kise, R., Cao, Y., Dwivedi-Agnihotri, H., Banerjee, R., Li, X.X., Cui, C.S., Lee, J.D., Kawakami, K., Maharana, J., Ranjan, A., Chaturvedi, M., Jhingan, G.D., Laporte, S.A., Woodruff, T.M., Inoue, A., Shukla, A.K. (2021). Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors. Mol Cell, 81, 4605-4621.
Peterson, Y.K., Luttrell, L.M. (2017). The diverse roles of arrestin scaffolds in G protein-coupled receptor signaling. Pharmacol Rev, 69, 256-297.
Pfeil, E.M., Brands, J., Merten, N., Vögtle, T., Vescovo, M., Rick, U., Albrecht, I.-M., Heycke, N., Kawakami, K., Ono, Y., Ngako Kadji, F.M., Hiratsuka, S., Aoki, J., Häberlein, F., Matthey, M., Garg, J., Hennen, S., Jobin, M.-L., Seier, K., Calebiro, D., Pfeifer, A., Heinemann, A., Wenzel, D., König, G.M., Nieswandt, B., Fleischmann, B.K., Inoue, A., Simon, K., Kostenis, E. (2020). Heterotrimeric G protein subunit Gαq is a master switch for Gβγ-mediated calcium mobilization by Gi-coupled GPCRs. Mol Cell, 80, 940-954.
Preininger, A.M., Meiler, J., Hamm, H.E. (2013). Conformational flexibility and structural dynamics in GPCR-mediated G protein activation: A perspective. J Mol Biol, 425, 2288-2298.
Qu, L., Pan, C., He, S.-M., Lang, B., Gao, G.-D., Wang, X.-L., Wang, Y. (2019). The Ras superfamily of small GTPases in non-neoplastic cerebral diseases. Front Mol Neurosci, 12, 121.
Rajagopal, S., Kim, J., Ahn, S., Craig, S., Lam, C.M., Gerard, N.P., Gerard, C., Lefkowitz, R.J. (2010). β-arrestin-but not G protein-mediated signaling by the aDecoya receptor CXCR7. Proc Natl Acad Sci USA, 107, 628-632.
Rasmussen, S.G.F., DeVree, B.T., Zou, Y., Kruse, A.C., Chung, K.Y., Kobilka, T.S., Thian, F.S., Chae, P.S., Pardon, E., Calinski, D., Mathiesen, J.M., Shah, S.T.A., Lyons, J.A., Caffrey, M., Gellman, S.H., Steyaert, J., Skiniotis, G., Weis, W.I., Sunahara, R.K., Kobilka, B.K. (2011). Crystal structure of the β2adrenergic receptor-Gs protein complex. Nature, 477, 549-555.
Rodbell, M., Birnbaumer, L., Pohl, S.L. Krans, H.M. (1971). The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. V. An obligatory role of guanyl nucleotides in glucagon action. J Biol Chem, 246, 1877-1882.
Ross, E.M. Gilman, A.G. (1977). Reconstitution of catecholamine-sensitive adenylate cyclase activity: Interactions of solubilized components with receptor-replete membranes. Proc Natl Acad Sci USA, 74, 3715-3719.
Samama, P., Cotecchia, S., Costa, T. Lefkowitz, R.J. (1993). A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model. J Biol Chem, 268, 4625-4636.
Schwindinger, W.F., Miric, A., Zimmerman, D., Levine, M.A. (1994). A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy uncouples cell surface receptors from adenylyl cyclase. J Biol Chem, 269, 25387-25391.
Sjögren, B. (2017). The evolution of regulators of G protein signalling proteins as drug targets a20 years in the making: IUPHAR review 21. Br J. Pharmacol, 174, 427-437.
Sleno, R., Hébert, T.E. (2019). Shaky ground aThe nature of metastable GPCR signalling complexes. Neuropharmacology, 152, 4-14.
Sprang, S.R. (2016). Invited review: Activation of G proteins by GTP and the mechanism of Gα-catalyzed GTP hydrolysis. Biopolymers, 105, 449-462.
Sriram, K., Insel, P.A. (2018). G protein-coupled receptors as targets for approved drugs: How many targets and how many drugs? Mol Pharmacol, 93, 251-258.
Sugino, S., Farrag, M. Ruiz-Velasco, V. (2016). Gα14 subunit-mediated inhibition of voltage-gated Ca2+and K+channels via neurokinin-1 receptors in rat celiac-superior mesenteric ganglion neurons. J Neurophysiol, 115, 1577-1586.
Sutherland, E.W., Robison, G.A. (1966). The role of cyclic-3a5a-AMP in responses to catecholamines and other hormones. Pharmacol Rev, 18, 145-161.
Sutherland, E.W. (1971). Studies on the mechanism of hormone action. Presented at the Nobel Prize lecture, Stockholm, Sweden.
Syrovatkina, V., Alegre, K.O., Dey, R., Huang, X.-Y. (2016). Regulation, signaling, and physiological functions of G-proteins. J Mol Biol, 428, 3850-3868.
Szpakowska, M., Nevins, A.M., Meyrath, M., Rhainds, D., Dahuys, T., Guité-Vinet, F., Dupuis, N., Gauthier, P.-A., Counson, M., Kleist, A., St-Onge, G., Hanson, J., Schols, D., Volkman, B.F., Heveker, N., Chevigné, A. (2018). Different contributions of chemokine N-terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3. Br J Pharmacol, 175, 1419-1438.
Tadevosyan, A., Vaniotis, G., Allen, B.G., Hébert, T.E., Nattel, S. (2012). G protein-coupled receptor signalling in the cardiac nuclear membrane: Evidence and possible roles in physiological and pathophysiological function. J Physiol, 590, 1313-1330.
Taussig, R., Tang, W.J., Hepler, J.R., Gilman, A.G. (1994). Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. J Biol Chem, 269, 6093-6100.
Tobin, A.B. (2008). G-protein-coupled receptor phosphorylation: Where, when and by whom. Br J Pharmacol, 153 (Suppl 1), S167-S176.
Van Eps, N., Preininger, A.M., Alexander, N., Kaya, A.I., Meier, S., Meiler, J., Hamm, H.E, Hubbell, W.L. (2011). Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit. Proc Natl Acad Sci USA, 108, 9420-9424.
Von Moo, E., Harpsøe, K., Hauser, A.S., Masuho, I., Bräuner-Osborne, H., Gloriam, D.E., Martemyanov, K.A. (2021). Ligand-directed bias of G protein signaling at the dopamine D2 receptor. Cell Chem Biol. https://doi.org/10.1016/j.chembiol.2021.07.004.
von Zastrow, M., Sorkin, A. (2021). Mechanisms for regulating and organizing receptor signaling by endocytosis. Annu Rev Biochem, 90, 709-737.
Wettschureck, N., Offermanns, S. (2005). Mammalian G proteins and their cell type specific functions. Physiol Rev, 85, 1159-1204.
Wong, Y.H., Conklin, B.R., Bourne, H.R. (1992). Gz-mediated hormonal inhibition of cyclic AMP accumulation. Science, 255, 339-342.
Worzfeld, T., Wettschureck, N., Offermanns, S. (2008). G(12)/G(13)-mediated signalling in mammalian physiology and disease. Trends Pharmacol Sci, 29, 582-589.
Wright, S.C. Bouvier, M. (2021). Illuminating the complexity of GPCR pathway selectivity aAdvances in biosensor development. Curr Opin Struct Biol, 69, 142-149.
Wright, S.C., Lukasheva, V., Le Gouill, C., Kobayashi, H., Breton, B., Mailhot-Larouche, S., Blondel-Tepaz, Ã., Antunes Vieira, N., Costa-Neto, C., Héroux, M., Lambert, N.A., Parreiras-E-Silva, L.T., Bouvier, M. (2021). BRET-based effector membrane translocation assay monitors GPCR-promoted and endocytosis-mediated Gq activation at early endosomes. Proc Natl Acad Sci USA, 118, e2025846118.
Yang, J., Wu, J., Kowalska, M.A., Dalvi, A., Prevost, N., OaBrien, P.J., Manning, D., Poncz, M., Lucki, I., Blendy, J.A. Brass, L.F. (2000). Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs. Proc Natl Acad Sci USA, 97, 9984-9989.
Yano, H., Cai, N.-S., Xu, M., Verma, R.K., Rea, W., Hoffman, A.F., Shi, L., Javitch, J.A., Bonci, A., Ferré, S. (2018). Gs-versus Golf-dependent functional selectivity mediated by the dopamine D1 receptor. Nat Commun, 9, 486.
Zhuang, X., Belluscio, L., Hen, R. (2000). Golfα mediates dopamine D1 receptor signaling. J Neurosci, 20, RC91 (1-5).
Zou, Q.-Y., Zhao, Y.-J., Zhou, C., Liu, A.-X., Zhong, X.-Q., Yan, Q., Li, Y., Yi, F.-X., Bird, I.M., Zheng, J. (2019). G Protein α subunit 14 mediates fibroblast growth factor 2-induced cellular responses in human endothelial cells. J Cell Physiol, 234, 10184-10195.