An integrated view on the role of receptor mosaics at perisynaptic level: focus on adenosine A_2A, dopamine D₂, cannabinoid CB₁, and metabotropic glutamate mGlu₅ receptors

References

• Agnati LF, Fuxe K. Aspects on the integrative capabilities of the central nervous system: evidence for “volume transmission” and its possible relevance for receptor–receptor interactions. In: Fuxe K, Agnati LF, eds. Receptor–Receptor Interactions. A New Intramembrane Integrative Mechanism. London: MacMillan, 1987, 236–49.
   Google Scholar
• Agnati LF, Ferrè S, Lluis C, Franco R, Fuxe K. Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons. Pharmacol Rev 2003, 55, 509–50.
   PubMed Web of Science ®Google Scholar
• Agnati LF, Santarossa L, Genedani S, Canela EI, Leo G, Franco R, et al. On the nested hierarchical organization of CNS: basic characteristics of neuronal molecular networks. In: Erdi P, Esposito A, Marinaro M, Scarpetta S, eds. Computational Neuroscience: Cortical Dynamics, Lecture Notes in Computer Sciences. Berlin, Heidelberg, New York: Springer, 2004, 24–54.
   Google Scholar
• Agnati LF, Leo G, Genedani S, Andreoli N, Marcellino D, Woods  A, et al. Structural plasticity in G-protein coupled receptors as demonstrated by the allosteric actions of homocysteine and computer-assisted analysis of disordered domains. Brain Res Rev 2008, 58, 459–74.
   PubMed Web of Science ®Google Scholar
• Jordan BA, Devi LA. G-protein-coupled receptor heterodimerization modulates receptor function. Nature 1999, 399, 697–700.
   PubMed Web of Science ®Google Scholar
• Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, et al. D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc Nat Acad Sci U S A 2007, 104, 654–9.
   PubMed Web of Science ®Google Scholar
• Agnati LF, Guidolin D, Leo G, Carone C, Genedani S, Fuxe K. Receptor–receptor interactions: a novel concept in brain integration. Prog Neurobiol. 2010, 90, 157–75.
   PubMed Web of Science ®Google Scholar
• Gurevich VV, Gurevich EV. Rich tapestry of G protein-coupled receptor signaling and regulatory mechanisms. Mol Pharmacol 2008, 74, 312–6.
   Web of Science ®Google Scholar
• Fuxe K, Agnati LF, Jacobsen K, Hillion J, Canals M, Torvinen M et al. Receptor heteromerization in adenosine A2A receptor signalling: relevance for striatal function and Parkinson’s disease. Neurology 2003, 61, S19–23.
   PubMedGoogle Scholar
• Fuxe K, Marcellino D, Rivera A, Diaz-Cabiale Z, Filip M, Gago  B, et al. Receptor–receptor interactions within receptor mosaics. Impact on neuropsychopharmacology. Brain Res Rev 2008, 58, 415–52.
   PubMedGoogle Scholar
• Fuxe K, Marcellino D, Guidolin D, Woods AS, Agnati LF. Heterodimers and receptor mosaics of different types of G-protein-coupled receptors. Physiology (Bethesda, Md) 2008, 23, 322–32.
   PubMed Web of Science ®Google Scholar
• Fuxe K, Marcellino D, Woods AS, Giuseppina L, Antonelli T, Ferraro L et al. Integrated signaling in heterodimers and receptor mosaics of different types of GPCRs of the forebrain: relevance for schizophrenia. J Neural Transm 2009, 116, 923–39.
   PubMed Web of Science ®Google Scholar
• Ferrè S, Agnati LF, Ciruela F, Lluis C, Woods AS, Fuxe K et al. Neurotransmitter receptor heteromers and their integrative role in ‘local modules’: the striatal spine module. Brain Res Rev 2007, 55, 55–67.
   PubMed Web of Science ®Google Scholar
• Carriba P, Navarro G, Ciruela F, Ferrè S, Casado V, Agnati L et al. Detection of heteromerization of more than two proteins by sequential BRET–FRET. Nat Methods 2008, 5, 727–33.
   PubMed Web of Science ®Google Scholar
• Cabello N, Gandía J, Bertarelli DC, Watanabe M, Lluís C, Franco  R, et al. Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher-order oligomers in living cells. J Neurochem 2009, 109, 1497–507.
   PubMed Web of Science ®Google Scholar
• Agnati LF, Guidolin D, Leo G, Fuxe K. A boolean network modelling of receptor mosaics, relevance of topology and cooperativity. J Neural Transm 2007, 114, 77–92.
   PubMed Web of Science ®Google Scholar
• Jansson A, Descarries L, Cornea-Hébert V, Riad M, Vergé D, Bancila M, et al. Transmitter–receptor mismatches in central dopamine, serotonin and neuropeptide systems. Further evidence for volume transmission. In: Walz W, ed. The Neuronal Environment: Brain Homeostasis in Health and Disease. Totowa, NJ: Humana Press 2001, 83–108.
   Google Scholar
• Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, et al. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 2002, 277, 18091–7.
   PubMed Web of Science ®Google Scholar
• Canals M, Marcellino D, Fanelli F, Ciruela F, De Benedetti P, Goldberg SR et al. Adenosine A2A–dopamine D2 receptor–receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 2003, 278, 46741–9.
   PubMed Web of Science ®Google Scholar
• Kamiya T, Saitoh O, Yoshioka K, Nakata H. Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Biochem Biophys Res Commun 2003, 306, 544–9.
   PubMed Web of Science ®Google Scholar
• Torvinen M, Kozell LB, Neve KA, Agnati LF, Fuxe K. Biochemical identification of the dopamine D2 receptor domains interacting with the adenosine A2A receptor. J Mol Neurosci 2004, 24, 173–80.
   Google Scholar
• Fuxe K, Ferrè S, Canals M, Torvinen M, Terasmaa A, Marcellino  D, et al. Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function. J Mol Neurosci 2005, 26, 209–20.
   PubMed Web of Science ®Google Scholar
• Fuxe K, Marcellino D, Genedani S, Agnati LF. Adenosine A(2A) receptors, dopamine D(2) receptors and their interactions in Parkinson’s disease. Mov Disord 2007, 22, 1990–2017.
   PubMed Web of Science ®Google Scholar
• Ferrè S, von Euler G, Johansson B, Fredholm BB, Fuxe K. Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc Nat Acad Sci U S A 1991, 88, 7238–41.
   PubMed Web of Science ®Google Scholar
• Fuxe K, Ferrè S, Zoli M, Agnati LF. Integrated events in central dopamine transmission as analyzed at multiple levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine A1/dopamine D1 receptor interactions in the basal ganglia. Brain Res Rev 1998, 26, 258–73.
   PubMedGoogle Scholar
• Diaz-Cabiale Z, Hurd Y, Guidolin D, Finnman UB, Zoli M, Agnati  LF, et al. Adenosine A2A agonist CGS 21680 decreases the affinity of dopamine D2 receptors for dopamine in human striatum. Neuroreport 2001, 12, 1831–4.
   PubMed Web of Science ®Google Scholar
• Hettinger BD, Lee A, Linden J, Rosin DL. Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum. J Comp Neurol 2001, 431, 331–46.
   PubMed Web of Science ®Google Scholar
• Ciruela F, Casadó V, Rodrigues RJ, Luján R, Burgueño J, Canals M et al. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 2006, 26, 2080–7.
   PubMed Web of Science ®Google Scholar
• Popoli P, Frank C, Tebano MT, Potenza RL, Pintor A, Domenici  MR, et al. Modulation of glutamate release and excitotoxicity by adenosine A2A receptors. Neurology 2003, 61, S69–71.
   PubMedGoogle Scholar
• Tanganelli S, Sandager Nielsen K, Ferraro L, Antonelli T, Kehr J, Franco R, et al. Striatal plasticity at the network level. Focus on adenosine A2A and D2 interactions in models of Parkinson’s disease. Parkinsonism Relat Disord 2004, 10, 273–80.
   PubMed Web of Science ®Google Scholar
• Fuxe K, Celani MF, Martire M, Zini I, Zoli M, Agnati LF. l-Glutamate reduces the affinity of [3H]N-propylnorapomorphine binding sites in striatal membranes. Eur J Pharmacol 1984, 100, 127–30.
   Google Scholar
• Ferré S, Popoli P, Rimondini R, Reggio R, Kehr J, Fuxe K. Adenosine A2A and group I metabotropic glutamate receptors synergistically modulate the binding characteristics of dopamine D2 receptors in the rat striatum. Neuropharmacology 1999, 38, 129–40.
   Google Scholar
• Popoli P, Pèzzola A, Torvinen M, Reggio R, Pintor A, Scarchilli L et al. 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, 505–13.
   PubMed Web of Science ®Google Scholar
• Rodrigues RJ, Alfaro TM, Rebola N, Oliveira CR, Cunha RA. Co-localization and functional interaction between adenosine A2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 2005, 92, 433–41.
   PubMed Web of Science ®Google Scholar
• Tebano MT, Martire A, Pepponi R, Domenici MR, 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, 619–25.
   Google Scholar
• Ferrè S, Karcz-Kubicha M, Hope BT, Popoli P, Burgueno J, Gutierrez MA et al. Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Nat Acad Sci U S A 2002, 99, 11940–5.
   PubMed Web of Science ®Google Scholar
• Díaz-Cabiale Z, Vivó M, Del Arco A, O’Connor WT, Harte MK, Müller CE et al. 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, 154–8.
   PubMed Web of Science ®Google Scholar
• Fuxe K, Ferrè S, Woods A, Rivera A, Hoistad M, Franco R, et al. Novel strategies for the treatment of Parkinson’s disease. Focus on receptor–receptor interactions in the basal ganglia. In: Kehr  J, Fuxe K, Ungerstedt U, Svensson T, eds. Monitoring Molecules in Neuroscience. Stockholm: Karolinska University Press, 2003, 199–202.
   Google Scholar
• Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M. Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci 2006, 29, 647–54.
   PubMed Web of Science ®Google Scholar
• Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M et al. Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 2008, 27, 2293–304.
   PubMed Web of Science ®Google Scholar
• Agnati LF, Fuxe K, Woods A, Genedani S, Guidolin D. Theoretical considerations on the topological organization of receptor mosaics. Curr Prot Pep Sci 2009, 10, 559–69.
   Google Scholar
• Kearn CS, Blake-Palmer K, Daniel E, Mackie K, Glass M. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk? Mol Pharmacol 2005, 67, 1697–704.
   PubMed Web of Science ®Google Scholar
• Marcellino D, Carriba P, Filip M, Borgkvist A, Frankowska M, Bellido I, et al. Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis. Neuropharmacology 2008, 54, 815–23.
   PubMedGoogle Scholar
• Glass M, Felder CC. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci 1997, 17, 5327–33.
   PubMed Web of Science ®Google Scholar
• Gonzalez B, Paz F, Florán L, Aceves J, Erlij D, Florán B. Cannabinoid agonists stimulate [3H]GABA release in the globus pallidus of the rat when G(i) protein-receptor coupling is restricted: role of dopamine D2 receptors. J Pharmacol Exp Ther 2009, 328, 822–8.
   Google Scholar
• Carriba P, Ortiz O, Patkar K, Justinova Z, Stroik J, Themann A, et al. Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 2007, 32, 2249–59.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay S, McIntosh HH, Houston DB, Howlett AC. The CB1 cannabinoid receptor juxtamembrane C-terminal peptide confers activation to specific G proteins in brain. Mol Pharmacol 2000, 57, 162–70.
   Google Scholar
• Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D. Dopamine activation of endogenous cannabinoid signalling in dorsal striatum. Nat Neurosci 1999, 2, 358–63.
   PubMed Web of Science ®Google Scholar
• Tarakanov AO, Fuxe KG. Triplet puzzle: homologies of receptor heteromers. J Mol Neurosci 2010, 41, 294–303.
   PubMed Web of Science ®Google Scholar
• Kull B, Ferré S, Arslan G, Svenningsson P, Fuxe K, Owman C et al. Reciprocal interactions between adenosine A2A and dopamine D2 receptors in Chinese hamster ovary cells co-transfected with the two receptors. Biochem Pharmacol 1999, 58, 1035–45.
   PubMed Web of Science ®Google Scholar
• Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn AC et al. Metabotropic mGlu5 receptors regulate adenosine A2A receptor signalling. Proc Natl Acad Sci U S A 2003, 100, 1322–7.
   Google Scholar
• Yang SN, Fior DR, Hedlund PB, Agnati LF, Fuxe K. Antagonistic regulation of alpha 2-adrenoceptors by neuropeptide Y receptor subtypes in the nucleus tractus solitarii. Eur J Pharmacol 1994, 271, 201–12.
   Google Scholar
• Yang SN, Fior DR, Hedlund PB, Agnati LF, Fuxe K. Selective modulation of the NPY receptors of the Y2 subtype by alpha 2 receptors in the nucleus tractus solitarii of the rat. A cardiovascular and quantitative receptor autoradiographical analysis. Brain Res 1994, 654,137–44.
   PubMed Web of Science ®Google Scholar
• Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z, Lohse MJ. Conformational cross-talk between alpha2A-adrenergic and mu-opioid receptors controls cell signalling. Nat Chem Biol 2008, 4, 126–31.
   PubMed Web of Science ®Google Scholar
• Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg AA et al. Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons. J Neurosci 2005, 25, 8432–8.
   PubMed Web of Science ®Google Scholar
• Borgkvist A, Marcellino D, Fuxe K, Greengard P, Fisone  G. Regulation of DARPP-32 phosphorylation by Delta9-tetrahydrocannabinol. Neuropharmacology 2007, 54, 31–5.
   Google Scholar
• Zezula J, Freissmuth M. The A(2A)-adenosine receptor: a GPCR with unique features? Br J Pharmacol 2008, 153, S184–90.
   PubMed Web of Science ®Google Scholar
• Agnati LF, Tarakanov AO, Ferré S, Fuxe K, Guidolin D. Receptor–receptor interactions, receptor mosaics, and basic principles of molecular network organization: possible implications for drug development. J Mol Neurosci 2005, 26, 193–208.
   PubMedGoogle Scholar
• Ciruela F, Albergaria C, Soriano A, Cuffí L, Carbonell L, Sánchez  S, Gandía J, Fernández-Dueñas V. Adenosine receptors interacting proteins (ARIPs): behind the biology of adenosine signaling. Biochim Biophys Acta 2010, 1798, 9–20.
   Web of Science ®Google Scholar
• Dunker AK, Brown CJ, Obradovic Z. Identification and functions of usefully disordered proteins. Adv Protein Chem 2002, 62, 25–49.
   PubMedGoogle Scholar
• Ferron F, Longhi S, Canard B, Karlin D. A practical overview of protein disorder prediction methods. Proteins 2006, 65, 1–14.
   PubMed Web of Science ®Google Scholar
• Sánchez de Groot N, Pallarés I, Avilés FX, Vendrell J, Ventura  S. Prediction of “hot spots” of aggregation in disease-linked polypeptides. BMC Struct Biol 2005, 5, 18.
   PubMed Web of Science ®Google Scholar
• Conchillo-Sole O, de Groot NS, Aviles FX, Vendrell J, Daura X, Ventura S. AGGRESCAN: a server for the prediction and evaluation of “hot spots” of aggregation in polypeptides. BMC Bioinformatics 2007, 8, 65.
   PubMed Web of Science ®Google Scholar
• Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982, 157, 105–32.
   PubMed Web of Science ®Google Scholar
• Eisenberg D. Three-dimensional structure of membrane and surface proteins. Ann Rev Biochem 1984, 53, 595–623.
   PubMed Web of Science ®Google Scholar
• Webb AR. Statistical Pattern Recognition, 2nd edition. John Wiley & Sons, New York, 2002.
   Google Scholar
• Filizola M, Weinstein H. The study of G-protein coupled receptor oligomerization with computational modeling and bioinformatics. FEBS J 2005, 272, 2926–38.
   PubMed Web of Science ®Google Scholar
• Jones S, Thornton JM. Prediction of protein–protein interaction sites using patch analysis. J Mol Biol 1997, 272, 133–43.
   PubMed Web of Science ®Google Scholar
• Huang B, Schroeder M. Using protein binding site prediction to improve protein docking. Gene 2008, 422, 14–21.
   PubMed Web of Science ®Google Scholar
• Lichtarge O, Bourne HR, Cohen FE. An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol 1996, 257, 342–58.
   PubMed Web of Science ®Google Scholar
• Ofran Y, Rost B. Predicted protein–protein interaction sites from local sequence information. FEBS Lett 2003, 544, 236–9.
   PubMed Web of Science ®Google Scholar
• Nemoto W, Toh H. Prediction of interfaces for oligomerizations of G-protein coupled receptors. Proteins 2005, 58, 644–60.
   PubMed Web of Science ®Google Scholar
• Zvelebil MJ, Barton GJ, Taylor WR, Sternberg MJ. Prediction of protein secondary structure and active sites using the alignment of homologous sequences. J Mol Biol 1987, 195, 957–61.
   PubMed Web of Science ®Google Scholar
• Nemoto W, Fukui K, Toh H. GRIP: a server for predicting interfaces for GPCR oligomerization. J Recept Signal Transduct Res 2009, 29, 312–7.
   PubMed Web of Science ®Google Scholar
• Guo W, Shi L, Javitch JA. The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J Biol Chem 2003, 278, 4385–8.
   PubMedGoogle Scholar
• Carrillo JJ, López-Giménez JF, Milligan G. Multiple interactions between transmembrane helices generate the oligomeric alpha1b-adrenoceptor. Mol Pharmacol 2004, 66, 1123–37.
   PubMed Web of Science ®Google Scholar
• Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y. Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics 2007, 8, 124–45.
   PubMed Web of Science ®Google Scholar
• Tobin AB, Butcher AJ, Kong KC. Location, location, location. site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling. Trends Pharmacol Sci 2008, 29, 413–20.
   PubMed Web of Science ®Google Scholar