Generic placeholder image

Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors

Author(s): David Agustín León-Navarro, José Luis Albasanz and Mairena Martín*

Volume 17, Issue 5, 2019

Page: [422 - 437] Pages: 16

DOI: 10.2174/1570159X16666180416093717

Price: $65


G-protein coupled receptors are transmembrane proteins widely expressed in cells and their transduction pathways are mediated by controlling second messenger levels through different G-protein interactions. Many of these receptors have been described as involved in the physiopathology of neurodegenerative diseases and even considered as potential targets for the design of novel therapeutic strategies. Endogenous and synthetic allosteric and orthosteric selective ligands are able to modulate GPCRs at both gene and protein expression levels and can also modify their physiological function. GPCRs that coexist in the same cells can homo- and heteromerize, therefore, modulating their function. Adenosine receptors are GPCRs which stimulate or inhibit adenylyl cyclase activity through Gi/Gs protein and are involved in the control of neurotransmitter release as glutamate. In turn, metabotropic glutamate receptors are also GPCRs which inhibit adenylyl cyclase or stimulate phospholipase C activities through Gi or Gq proteins, respectively. In recent years, evidence of crosstalk mechanisms between different GPCRs have been described. The aim of the present review was to summarize the described mechanisms of interaction and crosstalking between adenosine and metabotropic glutamate receptors, mainly of group I, in both in vitro and in vivo systems, and their possible use for the design of novel ligands for the treatment of neurodegenerative diseases.

Keywords: Metabotropic glutamate receptors, adenosine receptors, crosstalk, oligomerization, protein interaction, signalling.

Graphical Abstract
Cattaneo, F.; Guerra, G.; Parisi, M.; De Marinis, M.; Tafuri, D.; Cinelli, M.; Ammendola, R. Cell-surface receptors transactivation mediated by g protein-coupled receptors. Int. J. Mol. Sci., 2014, 15(11), 19700-19728. []. [PMID: 25356505].
Rivero-Müller A.; Jonas, K.C.; Hanyaloglu, A.C.; Huhtaniemi, I. Di/oligomerization of GPCRs-mechanisms and functional significance. Prog. Mol. Biol. Transl. Sci., 2013, 117, 163-185. []. [PMID: 23663969].
Rajagopal, S.; Shenoy, S.K. GPCR desensitization: Acute and prolonged phases. Cell. Signal., 2018, 41, 9-16. [PMID: 28137506].
Borroto-Escuela, D.O.; Brito, I.; Romero-Fernandez, W.; Di Palma, M.; Oflijan, J.; Skieterska, K.; Duchou, J.; Van Craenenbroeck, K.; Suárez-Boomgaard, D.; Rivera, A.; Guidolin, D.; Agnati, L.F.; Fuxe, K. The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components. Int. J. Mol. Sci., 2014, 15(5), 8570-8590. []. [PMID: 24830558].
Farran, B. An update on the physiological and therapeutic relevance of GPCR oligomers. Pharmacol. Res., 2017, 117, 303-327. []. [PMID: 28087443].
Dalet, F.G.; Guadalupe, T.F.; María Del Carmen, C.H.; Humberto, G.A.; Antonio, S.U. Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes. Neural Regen. Res., 2013, 8(24), 2290-2302. [PMID: 25206539].
Burford, N.T.; Wehrman, T.; Bassoni, D.; O’Connell, J.; Banks, M.; Zhang, L.; Alt, A. Identification of selective agonists and positive allosteric modulators for µ- and δ-opioid receptors from a single high-throughput screen. J. Biomol. Screen., 2014, 19(9), 1255-1265. []. [PMID: 25047277].
Chen, J.F.; Eltzschig, H.K.; Fredholm, B.B. Adenosine receptors as drug targets--what are the challenges? Nat. Rev. Drug Discov., 2013, 12(4), 265-286. []. [PMID: 23535933].
Ciruela, F.; Gómez-Soler, M.; Guidolin, D.; Borroto-Escuela, D.O.; Agnati, L.F.; Fuxe, K.; Fernández-Dueñas, V. Adenosine receptor containing oligomers: their role in the control of dopamine and glutamate neurotransmission in the brain. Biochim. Biophys. Acta, 2011, 1808(5), 1245-1255. []. [PMID: 21316336].
Nakata, H.; Suzuki, T.; Namba, K.; Oyanagi, K. Dimerization of G protein-coupled purinergic receptors: increasing the diversity of purinergic receptor signal responses and receptor functions. J. Recept. Signal Transduct. Res., 2010, 30(5), 337-346. []. [PMID: 20843271].
Fuxe, K.; Borroto-Escuela, D.O.; Marcellino, D.; Romero-Fernandez, W.; Frankowska, M.; Guidolin, D.; Filip, M.; Ferraro, L.; Woods, A.S.; Tarakanov, A.; Ciruela, F.; Agnati, L.F.; Tanganelli, S. GPCR heteromers and their allosteric receptor-receptor interactions. Curr. Med. Chem., 2012, 19(3), 356-363. []. [PMID: 22335512].
Franco, R.; Casadó, V.; Cortés, A.; Ferrada, C.; Mallol, J.; Woods, A.; Lluis, C.; Canela, E.I.; Ferré, S. Basic concepts in G-protein-coupled receptor homo- and heterodimerization. Sci. World J., 2007, 7, 48-57. []. [PMID: 17982576].
Zezula, J.; Freissmuth, M. The A(2A)-adenosine receptor: a GPCR with unique features? Br. J. Pharmacol., 2008, 153(Suppl. 1), S184-S190. []. [PMID: 18246094].
Julio-Pieper, M.; Flor, P.J.; Dinan, T.G.; Cryan, J.F. Exciting times beyond the brain: metabotropic glutamate receptors in peripheral and non-neural tissues. Pharmacol. Rev., 2011, 63(1), 35-58. []. [PMID: 21228260].
Pin, J.P.; Acher, F. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr. Drug Targets CNS Neurol. Disord., 2002, 1(3), 297-317. []. [PMID: 12769621].
Ribeiro, J.A.; Sebastião, A.M. Modulation and metamodulation of synapses by adenosine. Acta Physiol. (Oxf.), 2010, 199(2), 161-169. []. [PMID: 20345418].
Cunha, R.A. Neuroprotection by adenosine in the brain: From A(1) receptor activation to A (2A) receptor blockade. Purinergic Signal., 2005, 1(2), 111-134. []. [PMID: 18404497].
Hettinger, B.D.; Lee, A.; Linden, J.; Rosin, D.L. Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum. J. Comp. Neurol., 2001, 431(3), 331-346. [<331:AID-CNE1074>3.0.CO;2-W]. [PMID: 11170009].
Rebola, N.; Canas, P.M.; Oliveira, C.R.; Cunha, R.A. Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat. Neuroscience, 2005, 132(4), 893-903. []. [PMID: 15857695].
Ciruela, F.; Casadó, V.; Rodrigues, R.J.; Luján, R.; Burgueño, J.; Canals, M.; Borycz, J.; Rebola, N.; Goldberg, S.R.; Mallol, J.; Cortés, A.; Canela, E.I.; López-Giménez, J.F.; Milligan, G.; Lluis, C.; Cunha, R.A.; Ferré, S.; Franco, R. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J. Neurosci., 2006, 26(7), 2080-2087. []. [PMID: 16481441].
Ferré, S.; Agnati, L.F.; Ciruela, F.; Lluis, C.; Woods, A.S.; Fuxe, K.; Franco, R. Neurotransmitter receptor heteromers and their integrative role in ‘local modules’: the striatal spine module. Brain Res. Brain Res. Rev., 2007, 55(1), 55-67. []. [PMID: 17408563].
Cabello, N.; Gandía, J.; Bertarelli, D.C.; Watanabe, M.; Lluís, C.; Franco, R.; Ferré, S.; Luján, R.; Ciruela, F. Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher-order oligomers in living cells. J. Neurochem., 2009, 109(5), 1497-1507. []. [PMID: 19344374].
Bogenpohl, J.W.; Ritter, S.L.; Hall, R.A.; Smith, Y. Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum. J. Comp. Neurol., 2012, 520(3), 570-589. []. [PMID: 21858817].
Xie, J.D.; Chen, S.R.; Pan, H.L. Presynaptic mGluR5 receptor controls glutamatergic input through protein kinase C-NMDA receptors in paclitaxel-induced neuropathic pain. J. Biol. Chem., 2017, 292(50), 20644-20654. []. [PMID: 29074619].
Bragina, L.; Bonifacino, T.; Bassi, S.; Milanese, M.; Bonanno, G.; Conti, F. Differential expression of metabotropic glutamate and GABA receptors at neocortical glutamatergic and GABAergic axon terminals. Front. Cell. Neurosci., 2015, 9, 345. []. [PMID: 26388733].
Sheffler, D.J.; Gregory, K.J.; Rook, J.M.; Conn, P.J. Allosteric modulation of metabotropic glutamate receptors. Adv. Pharmacol., 2011, 62, 37-77. []. [PMID: 21907906].
Rodrigues, R.J.; Alfaro, T.M.; Rebola, N.; Oliveira, C.R.; Cunha, R.A. Co-localization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J. Neurochem., 2005, 92(3), 433-441. []. [PMID: 15659214].
Ogata, T.; Nakamura, Y.; Schubert, P. Potentiated cAMP rise in metabotropically stimulated rat cultured astrocytes by a Ca2+- related A1/A2 adenosine receptor cooperation. Eur. J. Neurosci., 1996, 8(6), 1124-1131. []. [PMID: 8752582].
Zhang, C.; Schmidt, J.T. Adenosine A1 and class II metabotropic glutamate receptors mediate shared presynaptic inhibition of retinotectal transmission. J. Neurophysiol., 1999, 82(6), 2947-2955. []. [PMID: 10601431].
Ogata, T.; Nakamura, Y.; Tsuji, K.; Shibata, T.; Kataoka, K.; Schubert, P. Adenosine enhances intracellular Ca2+ mobilization in conjunction with metabotropic glutamate receptor activation by t-ACPD in cultured hippocampal astrocytes. Neurosci. Lett., 1994, 170(1), 5-8. []. [PMID: 8041512].
Toms, N.J.; Roberts, P.J. Group 1 mGlu receptors elevate [Ca2+]i in rat cultured cortical type 2 astrocytes: [Ca2+]i synergy with adenosine A1 receptors. Neuropharmacology, 1999, 38(10), 1511-1517. []. [PMID: 10530813].
Ciruela, F.; Escriche, M.; Burgueno, J.; Angulo, E.; Casado, V.; Soloviev, M.M.; Canela, E.I.; Mallol, J.; Chan, W.Y.; Lluis, C.; McIlhinney, R.A.; Franco, R. Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes. J. Biol. Chem., 2001, 276(21), 18345-18351. []. [PMID: 11278325].
Kamikubo, Y.; Tabata, T.; Sakairi, H.; Hashimoto, Y.; Sakurai, T. Complex formation and functional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor. J. Pharmacol. Sci., 2015, 128(3), 125-130. []. [PMID: 26154847].
Albasanz, J.L.; León, D.; Ruíz, M.A.; Fernández, M.; Martín, M. Adenosine A1 receptor agonist treatment up-regulates rat brain metabotropic glutamate receptors. Biochim. Biophys. Acta, 2002, 1593(1), 69-75. []. [PMID: 12431785].
León, D.A.; Albasanz, J.L.; Castillo, C.A.; Iglesias, I.; Martín, M. Effect of chronic gestational treatment with the adenosine A1 receptor agonist R-phenylisopropyladenosine on metabotropic glutamate receptors/phospholipase C pathway in maternal and fetal brain. J. Neurosci. Res., 2008, 86(15), 3295-3305. []. [PMID: 18615645].
León, D.; Albasanz, J.L.; Castillo, C.A.; Martín, M. Effect of glutamate intake during gestation on adenosine A(1) receptor/adenylyl cyclase pathway in both maternal and fetal rat brain. J. Neurochem., 2008, 104(2), 435-445. [PMID: 17953672].
León, D.; Albasanz, J.L.; Ruíz, M.A.; Iglesias, I.; Martín, M. Effect of chronic gestational treatment with caffeine or theophylline on Group I metabotropic glutamate receptors in maternal and fetal brain. J. Neurochem., 2005, 94(2), 440-451. []. [PMID: 15998294].
Tabata, T.; Kawakami, D.; Hashimoto, K.; Kassai, H.; Yoshida, T.; Hashimotodani, Y.; Fredholm, B.B.; Sekino, Y.; Aiba, A.; Kano, M. G protein-independent neuromodulatory action of adenosine on metabotropic glutamate signalling in mouse cerebellar Purkinje cells. J. Physiol., 2007, 581(Pt 2), 693-708. []. [PMID: 17379632].
Kamikubo, Y.; Shimomura, T.; Fujita, Y.; Tabata, T.; Kashiyama, T.; Sakurai, T.; Fukurotani, K.; Kano, M. Functional cooperation of metabotropic adenosine and glutamate receptors regulates postsynaptic plasticity in the cerebellum. J. Neurosci., 2013, 33(47), 18661-18671. []. [PMID: 24259587].
Budd, D.C.; Nicholls, D.G. Protein kinase C-mediated suppression of the presynaptic adenosine A1 receptor by a facilitatory metabotropic glutamate receptor. J. Neurochem., 1995, 65(2), 615-621. []. [PMID: 7616216].
Shahraki, A.; Stone, T.W. Interactions between adenosine and metabotropic glutamate receptors in the rat hippocampal slice. Br. J. Pharmacol., 2003, 138(6), 1059-1068. []. [PMID: 12684261].
Díaz-Cabiale, Z.; Vivó, M.; Del Arco, A.; O’Connor, W.T.; Harte, M.K.; Müller, C.E.; Martínez, E.; Popoli, P.; Fuxe, K.; Ferré, S. Metabotropic glutamate mGlu5 receptor-mediated modulation of the ventral striopallidal GABA pathway in rats. Interactions with adenosine A(2A) and dopamine D(2) receptors. Neurosci. Lett., 2002, 324(2), 154-158. []. [PMID: 11988350].
Nishi, A.; Liu, F.; Matsuyama, S.; Hamada, M.; Higashi, H.; Nairn, A.C.; Greengard, P. Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc. Natl. Acad. Sci. USA, 2003, 100(3), 1322-1327. []. [PMID: 12538871].
Ferré, S.; Karcz-Kubicha, M.; Hope, B.T.; Popoli, P.; Burgueño, J.; Gutiérrez, M.A.; Casadó, V.; Fuxe, K.; Goldberg, S.R.; Lluis, C.; Franco, R.; Ciruela, F. Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc. Natl. Acad. Sci. USA, 2002, 99(18), 11940-11945. []. [PMID: 12189203].
Domenici, M.R.; Pepponi, R.; Martire, A.; Tebano, M.T.; Potenza, R.L.; Popoli, P. Permissive role of adenosine A2A receptors on metabotropic glutamate receptor 5 (mGluR5)-mediated effects in the striatum. J. Neurochem., 2004, 90(5), 1276-1279. []. [PMID: 15312183].
Tebano, M.T.; Martire, A.; Pepponi, R.; Domenici, M.R.; Popoli, P. Is the functional interaction between adenosine A(2A) receptors and metabotropic glutamate 5 receptors a general mechanism in the brain? Differences and similarities between the striatum and the hippocampus. Purinergic Signal., 2006, 2(4), 619-625. []. [PMID: 18404464].
Beggiato, S.; Tomasini, M.C.; Borelli, A.C.; Borroto-Escuela, D.O.; Fuxe, K.; Antonelli, T.; Tanganelli, S.; Ferraro, L. Functional role of striatal A2A, D2, and mGlu5 receptor interactions in regulating striatopallidal GABA neuronal transmission. J. Neurochem., 2016, 138(2), 254-264. []. [PMID: 27127992].
Popoli, P.; Pèzzola, A.; Torvinen, M.; Reggio, R.; Pintor, A.; Scarchilli, L.; Fuxe, K.; Ferré, S. The selective mGlu(5) receptor agonist CHPG inhibits quinpirole-induced turning in 6-hydroxydopamine-lesioned rats and modulates the binding characteristics of dopamine D(2) receptors in the rat striatum: interactions with adenosine A(2a) receptors. Neuropsychopharmacology, 2001, 25(4), 505-513. []. [PMID: 11557164].
Coccurello, R.; Breysse, N.; Amalric, M. Simultaneous blockade of adenosine A2A and metabotropic glutamate mGlu5 receptors increase their efficacy in reversing Parkinsonian deficits in rats. Neuropsychopharmacology, 2004, 29(8), 1451-1461. []. [PMID: 15039773].
Kachroo, A.; Orlando, L.R.; Grandy, D.K.; Chen, J.F.; Young, A.B.; Schwarzschild, M.A. Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J. Neurosci., 2005, 25(45), 10414-10419. []. [PMID: 16280580].
Brown, R.M.; Duncan, J.R.; Stagnitti, M.R.; Ledent, C.; Lawrence, A.J. mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine. Int. J. Neuropsychopharmacol., 2012, 15(7), 995-1001. []. [PMID: 21816123].
Adams, C.L.; Cowen, M.S.; Short, J.L.; Lawrence, A.J. Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats. Int. J. Neuropsychopharmacol., 2008, 11(2), 229-241. []. [PMID: 17517168].
Wright, S.R.; Zanos, P.; Georgiou, P.; Yoo, J.H.; Ledent, C.; Hourani, S.M.; Kitchen, I.; Winsky-Sommerer, R.; Bailey, A. A critical role of striatal A2A R-mGlu5 R interactions in modulating the psychomotor and drug-seeking effects of methamphetamine. Addict. Biol., 2016, 21(4), 811-825. []. [PMID: 25975203].
De Las Rivas, J.; Fontanillo, C. Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLOS Comput. Biol., 2010, 6(6), e1000807. []. [PMID: 20589078].
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. []. [PMID: 14597658].
Berman, H.; Henrick, K.; Nakamura, H. Announcing the worldwide protein data bank. Nat. Struct. Biol., 2003, 10(12), 980. []. [PMID: 14634627].
Guo, H.; An, S.; Ward, R.; Yang, Y.; Liu, Y.; Guo, X.X.; Hao, Q.; Xu, T.R. Methods used to study the oligomeric structure of G-protein-coupled receptors. Biosci. Rep., 2017, 37(2), BSR20160547. []. [PMID: 28062602].
Lohse, M.J. Dimerization in GPCR mobility and signaling. Curr. Opin. Pharmacol., 2010, 10(1), 53-58. []. [PMID: 19910252].
Sevastyanova, T.N.; Kammermeier, P.J. Cooperative signaling between homodimers of metabotropic glutamate receptors 1 and 5. Mol. Pharmacol., 2014, 86(5), 492-504. []. [PMID: 25113912].
Schonenbach, N.S.; Rieth, M.D.; Han, S.; O’Malley, M.A. Adenosine A2a receptors form distinct oligomers in protein detergent complexes. FEBS Lett., 2016, 590(18), 3295-3306. []. [PMID: 27543907].
El Moustaine, D.; Granier, S.; Doumazane, E.; Scholler, P.; Rahmeh, R.; Bron, P.; Mouillac, B.; Banères, J.L.; Rondard, P.; Pin, J.P. Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. Proc. Natl. Acad. Sci. USA, 2012, 109(40), 16342-16347. []. [PMID: 22988116].
Maurel, D.; Comps-Agrar, L.; Brock, C.; Rives, M.L.; Bourrier, E.; Ayoub, M.A.; Bazin, H.; Tinel, N.; Durroux, T.; Prézeau, L.; Trinquet, E.; Pin, J.P. Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization. Nat. Methods, 2008, 5(6), 561-567. []. [PMID: 18488035].
Doumazane, E.; Scholler, P.; Zwier, J.M.; Trinquet, E.; Rondard, P.; Pin, J.P. A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors. FASEB J., 2011, 25(1), 66-77. []. [PMID: 20826542].
Levitz, J.; Habrian, C.; Bharill, S.; Fu, Z.; Vafabakhsh, R.; Isacoff, E.Y. Mechanism of assembly and cooperativity of homomeric and heteromeric metabotropic glutamate receptors. Neuron, 2016, 92(1), 143-159. []. [PMID: 27641494].
Xue, L.; Rovira, X.; Scholler, P.; Zhao, H.; Liu, J.; Pin, J.P.; Rondard, P. Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer. Nat. Chem. Biol., 2015, 11(2), 134-140. []. [PMID: 25503927].
Ciruela, F.; Fernández-Dueñas, V.; Llorente, J.; Borroto-Escuela, D.; Cuffí, M.L.; Carbonell, L.; Sánchez, S.; Agnati, L.F.; Fuxe, K.; Tasca, C.I. G protein-coupled receptor oligomerization and brain integration: focus on adenosinergic transmission. Brain Res., 2012, 1476, 86-95. []. [PMID: 22575562].
Cabrera-Vera, T.M.; Vanhauwe, J.; Thomas, T.O.; Medkova, M.; Preininger, A.; Mazzoni, M.R.; Hamm, H.E. Insights into G protein structure, function, and regulation. Endocr. Rev., 2003, 24(6), 765-781. []. [PMID: 14671004].
Gomeza, J.; Mary, S.; Brabet, I.; Parmentier, M.L.; Restituito, S.; Bockaert, J.; Pin, J.P. Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists. Mol. Pharmacol., 1996, 50(4), 923-930. [PMID: 8863838].
Dhingra, A.; Lyubarsky, A.; Jiang, M.; Pugh, E.N., Jr; Birnbaumer, L.; Sterling, P.; Vardi, N. The light response of ON bipolar neurons requires G[alpha]o. J. Neurosci., 2000, 20(24), 9053-9058. []. [PMID: 11124982].
Waldhoer, M.; Wise, A.; Milligan, G.; Freissmuth, M.; Nanoff, C. Kinetics of ternary complex formation with fusion proteins composed of the A(1)-adenosine receptor and G protein alpha-subunits. J. Biol. Chem., 1999, 274(43), 30571-30579. []. [PMID: 10521440].
Soundararajan, M.; Willard, F.S.; Kimple, A.J.; Turnbull, A.P.; Ball, L.J.; Schoch, G.A.; Gileadi, C.; Fedorov, O.Y.; Dowler, E.F.; Higman, V.A.; Hutsell, S.Q.; Sundström, M.; Doyle, D.A.; Siderovski, D.P. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc. Natl. Acad. Sci. USA, 2008, 105(17), 6457-6462. []. [PMID: 18434541].
Snow, B.E.; Hall, R.A.; Krumins, A.M.; Brothers, G.M.; Bouchard, D.; Brothers, C.A.; Chung, S.; Mangion, J.; Gilman, A.G.; Lefkowitz, R.J.; Siderovski, D.P. GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain. J. Biol. Chem., 1998, 273(28), 17749-17755. []. [PMID: 9651375].
Roux, B.T.; Cottrell, G.S. G protein-coupled receptors: what a difference a ‘partner’ makes. Int. J. Mol. Sci., 2014, 15(1), 1112-1142. []. [PMID: 24441568].
Gracia, E.; Farré, D.; Cortés, A.; Ferrer-Costa, C.; Orozco, M.; Mallol, J.; Lluís, C.; Canela, E.I.; McCormick, P.J.; Franco, R.; Fanelli, F.; Casadó, V. The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors. FASEB J., 2013, 27(3), 1048-1061. []. [PMID: 23193172].
Franco, R.; Casadó, V.; Ciruela, F.; Saura, C.; Mallol, J.; Canela, E.I.; Lluis, C. Cell surface adenosine deaminase: much more than an ectoenzyme. Prog. Neurobiol., 1997, 52(4), 283-294. []. [PMID: 9247966].
Torvinen, M.; Ginés, S.; Hillion, J.; Latini, S.; Canals, M.; Ciruela, F.; Bordoni, F.; Staines, W.; Pedata, F.; Agnati, L.F.; Lluis, C.; Franco, R.; Ferré, S.; Fuxe, K. Interactions among adenosine deaminase, adenosine A(1) receptors and dopamine D(1) receptors in stably cotransfected fibroblast cells and neurons. Neuroscience, 2002, 113(3), 709-719. []. [PMID: 12150791].
Herrera, C.; Casadó, V.; Ciruela, F.; Schofield, P.; Mallol, J.; Lluis, C.; Franco, R. Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells. Mol. Pharmacol., 2001, 59(1), 127-134. []. [PMID: 11125033].
Málaga-Diéguez, L.; Yang, Q.; Bauer, J.; Pankevych, H.; Freissmuth, M.; Nanoff, C. Pharmacochaperoning of the A1 adenosine receptor is contingent on the endoplasmic reticulum. Mol. Pharmacol., 2010, 77(6), 940-952. []. [PMID: 20219842].
Brakeman, P.R.; Lanahan, A.A.; O’Brien, R.; Roche, K.; Barnes, C.A.; Huganir, R.L.; Worley, P.F. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature, 1997, 386(6622), 284-288. []. [PMID: 9069287].
Ango, F.; Prézeau, L.; Muller, T.; Tu, J.C.; Xiao, B.; Worley, P.F.; Pin, J.P.; Bockaert, J.; Fagni, L. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature, 2001, 411(6840), 962-965. []. [PMID: 11418862].
Ango, F.; Robbe, D.; Tu, J.C.; Xiao, B.; Worley, P.F.; Pin, J.P.; Bockaert, J.; Fagni, L. Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons. Mol. Cell. Neurosci., 2002, 20(2), 323-329. []. [PMID: 12093163].
Paquet, M.; Asay, M.J.; Fam, S.R.; Inuzuka, H.; Castleberry, A.M.; Oller, H.; Smith, Y.; Yun, C.C.; Traynelis, S.F.; Hall, R.A. The PDZ scaffold NHERF-2 interacts with mGluR5 and regulates receptor activity. J. Biol. Chem., 2006, 281(40), 29949-29961. []. [PMID: 16891310].
Ritter-Makinson, S.L.; Paquet, M.; Bogenpohl, J.W.; Rodin, R.E.; Chris Yun, C.; Weinman, E.J.; Smith, Y.; Hall, R.A. Group II metabotropic glutamate receptor interactions with NHERF scaffold proteins: Implications for receptor localization in brain. Neuroscience, 2017, 353, 58-75. []. [PMID: 28392297].
Enz, R. The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7. FEBS Lett., 2002, 514(2-3), 184-188. []. [PMID: 11943148].
Canela, L.; Luján, R.; Lluís, C.; Burgueño, J.; Mallol, J.; Canela, E.I.; Franco, R.; Ciruela, F. The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface expression and function of the receptor. Mol. Cell. Neurosci., 2007, 36(1), 1-12. []. [PMID: 17689978].
Canela, L.; Fernández-Dueñas, V.; Albergaria, C.; Watanabe, M.; Lluís, C.; Mallol, J.; Canela, E.I.; Franco, R.; Luján, R.; Ciruela, F. The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function. J. Neurochem., 2009, 111(2), 555-567. []. [PMID: 19694902].
Uematsu, K.; Heiman, M.; Zelenina, M.; Padovan, J.; Chait, B.T.; Aperia, A.; Nishi, A.; Greengard, P. Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function. J. Neurochem., 2015, 132(6), 677-686. []. [PMID: 25639954].
Palmer, T.M.; Stiles, G.L. Stimulation of A(2A) adenosine receptor phosphorylation by protein kinase C activation: evidence for regulation by multiple protein kinase C isoforms. Biochemistry, 1999, 38(45), 14833-14842. []. [PMID: 10555965].
Cartmell, J.; Goepfert, F.; Knoflach, F.; Pink, J.R.; Bleuel, Z.; Richards, J.G.; Schaffhauser, H.; Kemp, J.A.; Wichmann, J.; Mutel, V. Effect of metabotropic glutamate receptor activation on receptor-mediated cyclic AMP responses in primary cultures of rat striatal neurones. Brain Res., 1998, 791(1-2), 191-199. []. [PMID: 9593890].
de Mendonça, A.; Ribeiro, J.A. Influence of metabotropic glutamate receptor agonists on the inhibitory effects of adenosine A1 receptor activation in the rat hippocampus. Br. J. Pharmacol., 1997, 121(8), 1541-1548. []. [PMID: 9283686].
Macek, T.A.; Schaffhauser, H.; Conn, P.J. Protein kinase C and A3 adenosine receptor activation inhibit presynaptic metabotropic glutamate receptor (mGluR) function and uncouple mGluRs from GTP-binding proteins. J. Neurosci., 1998, 18(16), 6138-6146. []. [PMID: 9698308].
Minakami, R.; Jinnai, N.; Sugiyama, H. Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5 (mGluR5) are antagonistic in vitro. J. Biol. Chem., 1997, 272(32), 20291-20298. []. [PMID: 9242710].
Saugstad, J.A.; Yang, S.; Pohl, J.; Hall, R.A.; Conn, P.J. Interaction between metabotropic glutamate receptor 7 and alpha tubulin. J. Neurochem., 2002, 80(6), 980-988. []. [PMID: 11953448].
Lidwell, K.; Dillon, J.; Sihota, A.; O’Connor, V.; Pilkington, B. Determining calmodulin binding to metabotropic glutamate receptors with distinct protein-interaction methods. Biochem. Soc. Trans., 2004, 32(Pt 5), 868-870. []. [PMID: 15494036].
El Far, O.; Betz, H. G-protein-coupled receptors for neurotransmitter amino acids: C-terminal tails, crowded signalosomes. Biochem. J., 2002, 365(Pt 2), 329-336. []. [PMID: 12006104].
Ko, S.J.; Isozaki, K.; Kim, I.; Lee, J.H.; Cho, H.J.; Sohn, S.Y.; Oh, S.R.; Park, S.; Kim, D.G.; Kim, C.H.; Roche, K.W. PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A. J. Neurosci., 2012, 32(46), 16391-16401. []. [PMID: 23152621].
Nakajima, Y.; Yamamoto, T.; Nakayama, T.; Nakanishi, S. A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7. J. Biol. Chem., 1999, 274(39), 27573-27577. []. [PMID: 10488094].
El Far, O.; Bofill-Cardona, E.; Airas, J.M.; O’Connor, V.; Boehm, S.; Freissmuth, M.; Nanoff, C.; Betz, H. Mapping of calmodulin and Gbetagamma binding domains within the C-terminal region of the metabotropic glutamate receptor 7A. J. Biol. Chem., 2001, 276(33), 30662-30669. []. [PMID: 11395497].
Sorensen, S.D.; Macek, T.A.; Cai, Z.; Saugstad, J.A.; Conn, P.J. Dissociation of protein kinase-mediated regulation of metabotropic glutamate receptor 7 (mGluR7) interactions with calmodulin and regulation of mGluR7 function. Mol. Pharmacol., 2002, 61(6), 1303-1312. []. [PMID: 12021391].
Navarro, G.; Aymerich, M.S.; Marcellino, D.; Cortés, A.; Casadó, V.; Mallol, J.; Canela, E.I.; Agnati, L.; Woods, A.S.; Fuxe, K.; Lluís, C.; Lanciego, J.L.; Ferré, S.; Franco, R. Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors. J. Biol. Chem., 2009, 284(41), 28058-28068. []. [PMID: 19632986].
Kitano, J.; Kimura, K.; Yamazaki, Y.; Soda, T.; Shigemoto, R.; Nakajima, Y.; Nakanishi, S. Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. J. Neurosci., 2002, 22(4), 1280-1289. []. [PMID: 11850456].
Gsandtner, I.; Charalambous, C.; Stefan, E.; Ogris, E.; Freissmuth, M.; Zezula, J. Heterotrimeric G protein-independent signaling of a G protein-coupled receptor. Direct binding of ARNO/cytohesin-2 to the carboxyl terminus of the A2A adenosine receptor is necessary for sustained activation of the ERK/MAP kinase pathway. J. Biol. Chem., 2005, 280(36), 31898-31905. []. [PMID: 16027149].
Francesconi, A.; Duvoisin, R.M. Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain. Proc. Natl. Acad. Sci. USA, 2000, 97(11), 6185-6190. []. [PMID: 10823959].
Dev, K.K.; Nakajima, Y.; Kitano, J.; Braithwaite, S.P.; Henley, J.M.; Nakanishi, S. PICK1 interacts with and regulates PKC phosphorylation of mGLUR7. J. Neurosci., 2000, 20(19), 7252-7257. []. [PMID: 11007882].
Dev, K.K.; Nakanishi, S.; Henley, J.M. The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands. J. Biol. Chem., 2004, 279(40), 41393-41397. []. [PMID: 15247289].
Hirbec, H.; Perestenko, O.; Nishimune, A.; Meyer, G.; Nakanishi, S.; Henley, J.M.; Dev, K.K. The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. J. Biol. Chem., 2002, 277(18), 15221-15224. []. [PMID: 11891216].
Boudin, H.; Doan, A.; Xia, J.; Shigemoto, R.; Huganir, R.L.; Worley, P.; Craig, A.M. Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site. Neuron, 2000, 28(2), 485-497. []. [PMID: 11144358].
Thompson, J.W.; Nagel, J.; Hoving, S.; Gerrits, B.; Bauer, A.; Thomas, J.R.; Kirschner, M.W.; Schirle, M.; Luchansky, S.J. Quantitative Lys-ϵ-Gly-Gly (diGly) proteomics coupled with inducible RNAi reveals ubiquitin-mediated proteolysis of DNA damage-inducible transcript 4 (DDIT4) by the E3 ligase HUWE1. J. Biol. Chem., 2014, 289(42), 28942-28955. []. [PMID: 25147182].
Wagner, S.A.; Beli, P.; Weinert, B.T.; Nielsen, M.L.; Cox, J.; Mann, M.; Choudhary, C. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol. Cell. Proteomics, 2011, 10(10), M111-M013284.
Danielsen, J.M.; Sylvestersen, K.B.; Bekker-Jensen, S.; Szklarczyk, D.; Poulsen, J.W.; Horn, H.; Jensen, L.J.; Mailand, N.; Nielsen, M.L. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Mol. Cell. Proteomics, 2011, 10(3), M110-M003590. [].
Dores, M.R.; Trejo, J. Atypical regulation of G protein-coupled receptor intracellular trafficking by ubiquitination. Curr. Opin. Cell Biol., 2014, 27, 44-50. []. [PMID: 24680429].
Whistler, J.L.; Enquist, J.; Marley, A.; Fong, J.; Gladher, F.; Tsuruda, P.; Murray, S.R.; Von Zastrow, M. Modulation of postendocytic sorting of G protein-coupled receptors. Science, 2002, 297(5581), 615-620. []. [PMID: 12142540].
Heydorn, A.; Søndergaard, B.P.; Ersbøll, B.; Holst, B.; Nielsen, F.C.; Haft, C.R.; Whistler, J.; Schwartz, T.W. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP). J. Biol. Chem., 2004, 279(52), 54291-54303. []. [PMID: 15452121].
Schonenbach, N.S.; Hussain, S.; O’Malley, M.A. Structure and function of G protein-coupled receptor oligomers: implications for drug discovery. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2015, 7(3), 408-427. []. [PMID: 25521522].
Ferré, S.; Casadó, V.; Devi, L.A.; Filizola, M.; Jockers, R.; Lohse, M.J.; Milligan, G.; Pin, J.P.; Guitart, X. G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol. Rev., 2014, 66(2), 413-434. []. [PMID: 24515647].
Gracia, E.; Moreno, E.; Cortés, A.; Lluís, C.; Mallol, J.; McCormick, P.J.; Canela, E.I.; Casadó, V. Homodimerization of adenosine A1 receptors in brain cortex explains the biphasic effects of caffeine. Neuropharmacology, 2013, 71, 56-69. []. [PMID: 23523559].
Ferre, S.; von Euler, G.; Johansson, B.; Fredholm, B.B.; Fuxe, K. Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc. Natl. Acad. Sci. USA, 1991, 88(16), 7238-7241. []. [PMID: 1678519].
Kühhorn, J.; Hübner, H.; Gmeiner, P. Bivalent dopamine D2 receptor ligands: synthesis and binding properties. J. Med. Chem., 2011, 54(13), 4896-4903. []. [PMID: 21599022].
Borroto-Escuela, D.O.; Pintsuk, J.; Schäfer, T.; Friedland, K.; Ferraro, L.; Tanganelli, S.; Liu, F.; Fuxe, K. Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia. Ther. Adv. Psychopharmacol., 2016, 6(2), 77-94. []. [PMID: 27141290].
Shen, J.; Zhang, L.; Song, W.L.; Meng, T.; Wang, X.; Chen, L.; Feng, L.Y.; Xu, Y.C.; Shen, J.K. Design, synthesis and biological evaluation of bivalent ligands against A(1)-D(1) receptor heteromers. Acta Pharmacol. Sin., 2013, 34(3), 441-452. []. [PMID: 23334237].
Soriano, A.; Ventura, R.; Molero, A.; Hoen, R.; Casadó, V.; Cortés, A.; Fanelli, F.; Albericio, F.; Lluís, C.; Franco, R.; Royo, M. Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A2A-D2 receptor heteromers. J. Med. Chem., 2009, 52(18), 5590-5602. []. [PMID: 19711895].
Peterson, C.D.; Kitto, K.F.; Akgün, E.; Lunzer, M.M.; Riedl, M.S.; Vulchanova, L.; Wilcox, G.L.; Portoghese, P.S.; Fairbanks, C.A. Bivalent ligand that activates mu opioid receptor and antagonizes mGluR5 receptor reduces neuropathic pain in mice. Pain, 2017, 158(12), 2431-2441. []. [PMID: 28891868].
Hasbi, A.; O’Dowd, B.F.; George, S.R. Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance. Mol. Brain, 2011, 4, 26. []. [PMID: 21663703].
Bhattacharyya, S. Inside story of Group I Metabotropic Glutamate Receptors (mGluRs) Int. J. Biochem. Cell Biol., 2016, 77 (Pt B), 205-12.
Cordomí, A.; Navarro, G.; Aymerich, M.S.; Franco, R. Structures for G-protein-coupled receptor tetramers in complex with G Proteins. Trends Biochem. Sci., 2015, 40(10), 548-551. []. [PMID: 26410595].
Navarro, G.; Cordomí, A.; Zelman-Femiak, M.; Brugarolas, M.; Moreno, E.; Aguinaga, D.; Perez-Benito, L.; Cortés, A.; Casadó, V.; Mallol, J.; Canela, E.I.; Lluís, C.; Pardo, L.; García-Sáez, A.J.; McCormick, P.J.; Franco, R. Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs. BMC Biol., 2016, 14, 26. []. [PMID: 27048449].

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy