395
Views
19
CrossRef citations to date
0
Altmetric
Review Article

Possible new targets for GPCR modulation: allosteric interactions, plasma membrane domains, intercellular transfer and epigenetic mechanisms

, , , , , , , , , & show all
Pages 315-331 | Received 26 May 2011, Accepted 20 Jun 2011, Published online: 19 Sep 2011

References

  • Rees S, Morrow D, Kenakin T. GPCR drug discovery through the exploitation of allosteric drug binding sites. Receptors Channels 2002, 8, 261–268.
  • Cho DI, Zheng M, Kim KM. Current perspectives on the selective regulation of dopamine D2 and D3 receptors. Arch Pharm Res 2010, 33, 1521–1538.
  • Moreira FA, Crippa JA. The psychiatric side-effects of rimonabant. Rev Bras Psiquiatr 2009, 31, 145–153.
  • Buhmann C, Klucken J, Korchounov A, Schwarz M, Vieregge P, Jost WH. When should we start medical treatment in Parkinson disease. Fortschr Neurol Psychiatr 2010, 78 Suppl 1, S31–S33.
  • Kitano H. A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov 2007, 6, 202–210.
  • Ahlquist RP. A study of the adrenotropic receptors. Am J Physiol 1948, 153, 586–600.
  • Agnati LF, Fuxe K, Zini I, Lenzi P, Hökfelt T. Aspects on receptor regulation and isoreceptor identification. Med Biol 1980, 58, 182–187.
  • Covelli V, Memo M, Spano PF, Trabucchi M. Characterization of dopamine receptors in various species of invertebrates and vertebrates. Neuroscience 1981, 6, 2077–2079.
  • Missale C, Memo M, Liberini P, Carruba MO, Spano P. Evidence for the presence of D1 and D2 dopamine receptors in the rat adrenal cortex. Eur J Pharmacol 1985, 109, 315–316.
  • Agnati LF, Guidolin D, Guescini M, Genedani S, Fuxe K. Understanding wiring and volume transmission. Brain Res Rev 2010, 64, 137–159.
  • Agnati LF, Fuxe K. New concepts on the structure of the neuronal networks: the miniaturization and hierarchical organization of the central nervous system. (Hypothesis). Biosci Rep 1984, 4, 93–98.
  • Agnati LF, Guidolin D, Carone C, Dam M, Genedani S, Fuxe K. Understanding neuronal molecular networks builds on neuronal cellular network architecture. Brain Res Rev 2008, 58, 379–399.
  • Kenakin T. G protein coupled receptors as allosteric proteins and the role of allosteric modulators. J Recept Signal Transduct Res 2010, 30, 313–321.
  • Kenakin TP. Ligand detection in the allosteric world. J Biomol Screen 2010, 15, 119–130.
  • Agnati LF, Leo G, Genedani S, Andreoli N, Marcellino D, Woods A, Piron L, Guidolin D, Fuxe K. 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, 459–474.
  • Goodey NM, Benkovic SJ. Allosteric regulation and catalysis emerge via a common route. Nat Chem Biol 2008, 4, 474–482.
  • Pauling L. Protein interactions. Aggregation of globular proteins. Discussions Faraday Soc 1953, 13, 170–176.
  • Monod J, Changeux JP, Jacob F. Allosteric proteins and cellular control systems. J Mol Biol 1963, 6, 306–329.
  • Monod J, Wyman J, Changeux JP. On the nature of allosteric transitions: a plausible model. J Mol Biol 1965, 12, 88–118.
  • Fenton AW. Allostery: an illustrated definition for the ‘second secret of life’. Trends Biochem Sci 2008, 33, 420–425.
  • Gunasekaran K, Ma B, Nussinov R. Is allostery an intrinsic property of all dynamic proteins? Proteins 2004, 57, 433–443.
  • Del Sol A, Araúzo-Bravo MJ, Amoros D, Nussinov R. Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Genome Biol 2007, 8, R92.
  • Tsai CJ, Del Sol A, Nussinov R. Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms. Mol Biosyst 2009, 5, 207–216.
  • Whitty A. Cooperativity and biological complexity. Nat Chem Biol 2008, 4, 435–439.
  • Petsko GA., Ringe D. Protein Structure and Function. London: New Science Press (2004).
  • Monod, J. Chance and Necessity: Essay on the Natural Philosophy of Modern Biology. Penguin Books (1977).
  • Kenakin T. Allosteric theory: taking therapeutic advantage of the malleable nature of GPCRs. Curr Neuropharmacol 2007, 5, 149–156.
  • Kenakin TP. ‘7TM receptor allostery: putting numbers to shapeshifting proteins. Trends Pharmacol Sci 2009, 30, 460–469.
  • Bridges TM, Lindsley CW. G-protein-coupled receptors: from classical modes of modulation to allosteric mechanisms. ACS Chem Biol 2008, 3, 530–541.
  • Wang L, Martin B, Brenneman R, Luttrell LM, Maudsley S. Allosteric modulators of g protein-coupled receptors: future therapeutics for complex physiological disorders. J Pharmacol Exp Ther 2009, 331, 340–348.
  • Goodsell DS, Olson AJ. Structural symmetry and protein function. Annu Rev Biophys Biomol Struct 2000, 29, 105–153.
  • Fuxe K, Agnati LF. Receptor-Receptor Interactions: A New Intramembrane Integrative Mechanism. MacMillan Press, London (1987).
  • Süel GM, Lockless SW, Wall MA, Ranganathan R. Evolutionarily conserved networks of residues mediate allosteric communication in proteins. Nat Struct Biol 2003, 10, 59–69.
  • 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, 157–175.
  • Daily MD, Gray JJ. Allosteric communication occurs via networks of tertiary and quaternary motions in proteins. PLoS Comput Biol 2009, 5, e1000293.
  • Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE, Okamoto T, Lisanti MP. Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 1999, 19, 7289–7304.
  • Agnati LF, Fuxe K, Ferré S. How receptor mosaics decode transmitter signals. Possible relevance of cooperativity. Trends Biochem Sci 2005, 30, 188–193.
  • Agnati LF, Santarossa L, Genedani S, Canela EI, Leo G, Franco R, Woods A, Lluis C, Ferrè S, Fuxe K. On the nested hierarchical organization of CNS: basic characteristics of neuronal molecular networks In: Computational Neuroscience: cortical dynamycs, Lecture Notes in Computer Sciences, Erdi P., Esposito A., Marinaro M., Scarpetta S. (Eds.), Berlin Heidelberg New York: Springer 2004, 24–54.
  • Rozenfeld R, Devi LA. Exploring a role for heteromerization in GPCR signalling specificity. Biochem J 2010, 433, 11–18.
  • Agnati LF, Fuxe K, Zoli M, Rondanini C, Ogren SO. New vistas on synaptic plasticity: the receptor mosaic hypothesis of the engram. Med Biol 1982, 60, 183–190.
  • Agnati LF, Franzen O, Ferré S, Leo G, Franco R, Fuxe K. Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia. J Neural Transm Suppl 2003, 65, 1–28.
  • Agnati LF, Guidolin D, Vilardaga JP, Ciruela F, Fuxe K. On the expanding terminology in the GPCR field: the meaning of receptor mosaics and receptor heteromers. J Recept Signal Transduct Res 2010, 30, 287–303.
  • Fuxe K, Marcellino D, Borroto-Escuela DO, Frankowska M, Ferraro L, Guidolin D, Ciruela F, Agnati LF. The changing world of G protein-coupled receptors: from monomers to dimers and receptor mosaics with allosteric receptor-receptor interactions. J Recept Signal Transduct Res 2010, 30, 272–283.
  • Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z, Lohse MJ. Conformational cross-talk between alpha2A-adrenergic and mu-opioid receptors controls cell signaling. Nat Chem Biol 2008, 4, 126–131.
  • Lindner R, Naim HY. Domains in biological membranes. Exp Cell Res 2009, 315, 2871–2878.
  • Shaikh SR, Rockett BD, Salameh M, Carraway K. Docosahexaenoic acid modifies the clustering and size of lipid rafts and the lateral organization and surface expression of MHC class I of EL4 cells. J Nutr 2009, 139, 1632–1639.
  • Negro A, Dodge-Kafka K, Kapiloff MS. Signalosomes as Therapeutic Targets. Prog Pediatr Cardiol 2008, 25, 51–56.
  • Agnati LF, Guidolin D, Fuxe K. The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology. J Neural Transm 2007, 114, 3–19.
  • 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.
  • Herrera JL, Diaz M, Hernández-Fernaud JR, Salido E, Alonso R, Fernández C, Morales A, Marin R. Voltage-dependent anion channel as a resident protein of lipid rafts: post-transductional regulation by estrogens and involvement in neuronal preservation against Alzheimer’s disease. J Neurochem 2011, 116, 820–827.
  • Garlid KD, Costa AD, Quinlan CL, Pierre SV, Dos Santos P. Cardioprotective signaling to mitochondria. J Mol Cell Cardiol 2009, 46, 858–866.
  • Spörl F, Wunderskirchner M, Ullrich O, Bömke G, Breitenbach U, Blatt T, Wenck H, Wittern KP, Schrader A. Real-time monitoring of membrane cholesterol reveals new insights into epidermal differentiation. J Invest Dermatol 2010, 130, 1268–1278.
  • Lombardi D, Cuenoud B, Krämer SD. Lipid membrane interactions of indacaterol and salmeterol: do they influence their pharmacological properties? Eur J Pharm Sci 2009, 38, 533–547.
  • Milligan G, Smith NJ. Allosteric modulation of heterodimeric G-protein-coupled receptors. Trends Pharmacol Sci 2007, 28, 615–620.
  • Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972, 175, 720–731.
  • Ernst AM, Contreras FX, Brügger B, Wieland F. Determinants of specificity at the protein-lipid interface in membranes. FEBS Lett 2010, 584, 1713–1720.
  • Lübke J, Feldmeyer D. Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex. Brain Struct Funct 2007, 212, 3–17.
  • Goldman-Rakic L. Local circuit neurons. Neurosci Res Prog Bull 1975, 13, 299–31.
  • Bethani I, Skånland SS, Dikic I, Acker-Palmer A. Spatial organization of transmembrane receptor signalling. EMBO J 2010, 29, 2677–2688.
  • Ohno-Iwashita Y, Shimada Y, Hayashi M, Inomata M. Plasma membrane microdomains in aging and disease. Geriatr Gerontol Int 2010, 10 Suppl 1, S41–S52.
  • Alemany R, Perona JS, Sánchez-Dominguez JM, Montero E, Cañizares J, Bressani R, Escribá PV, Ruiz-Gutierrez V. G protein-coupled receptor systems and their lipid environment in health disorders during aging. Biochim Biophys Acta 2007, 1768, 964–975.
  • Horváth I, Multhoff G, Sonnleitner A, Vígh L. Membrane-associated stress proteins: more than simply chaperones. Biochim Biophys Acta 2008, 1778, 1653–1664.
  • Hunte C. Specific protein-lipid interactions in membrane proteins. Biochem Soc Trans 2005, 33, 938–942.
  • Rodbell M. The complex regulation of receptor-coupled G-proteins. Adv Enzyme Regul 1997, 37, 427–435.
  • Zhang L, Yang S, Huang Y. Evidence for disaggregation of oligomeric G(o)alpha induced by guanosine-5;-3-O-(thio)triphosphate activation. Biochemistry Mosc 2003, 68, 121–128.
  • 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.
  • Luttrell LM. Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors. Mol Biotechnol 2008, 39, 239–264.
  • Yáñez-Mó M, Barreiro O, Gordon-Alonso M, Sala-Valdés M, Sánchez-Madrid F. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol 2009, 19, 434–446.
  • Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E. Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J 2009, 420, 133–154.
  • Boucheix C, Rubinstein E. Tetraspanins. Cell Mol Life Sci 2001, 58, 1189–1205.
  • Little KD, Hemler ME, Stipp CS. Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell 2004, 15, 2375–2387.
  • Rana S, Zöller M. Exosome target cell selection and the importance of exosomal tetraspanins: a hypothesis. Biochem Soc Trans 2011, 39, 559–562.
  • Guescini M, Genedani S, Stocchi V, Agnati LF. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm 2010, 117, 1–4.
  • Guescini M, Guidolin D, Vallorani L, Casadei L, Gioacchini AM, Tibollo P, Battistelli M, Falcieri E, Battistin L, Agnati LF, Stocchi V. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp Cell Res 2010, 316, 1977–1984.
  • Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol 2009, 19, 43–51.
  • Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 2009, 9, 581–593.
  • Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 2009, 21, 575–581.
  • Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 2010, 78, 838–848.
  • Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics 2010, 73, 1907–1920.
  • Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J. Microvesicles as mediators of intercellular communication in cancer-the emerging science of cellular ‘debris’. Semin Immunopathol 2011 , Feb 12.
  • Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K. Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci USA 2006, 103, 11172–11177.
  • Vingtdeux V, Hamdane M, Loyens A, Gelé P, Drobeck H, Bégard S, Galas MC, Delacourte A, Beauvillain JC, Buée L, Sergeant N. Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies. J Biol Chem 2007, 282, 18197–18205.
  • Sharples RA, Vella LJ, Nisbet RM, Naylor R, Perez K, Barnham KJ, Masters CL, Hill AF. Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes. FASEB J 2008, 22, 1469–1478.
  • Ghidoni R, Paterlini A, Albertini V, Glionna M, Monti E, Schiaffonati L, Benussi L, Levy E, Binetti G. Cystatin C is released in association with exosomes: A new tool of neuronal communication which is unbalanced in Alzheimer’s disease. Neurobiol Aging 2011, 32, 1435–1442.
  • Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007, 9, 654–659.
  • Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008, 10, 1470–1476.
  • Quah BJ, Barlow VP, McPhun V, Matthaei KI, Hulett MD, Parish CR. Bystander B cells rapidly acquire antigen receptors from activated B cells by membrane transfer. Proc Natl Acad Sci USA 2008, 105, 4259–4264.
  • Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res 2005, 11, 1010–1020.
  • Calzolari A, Raggi C, Deaglio S, Sposi NM, Stafsnes M, Fecchi K, Parolini I, Malavasi F, Peschle C, Sargiacomo M, Testa U. TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway. J Cell Sci 2006, 119, 4486–4498.
  • Fagiolini M, Jensen CL, Champagne FA. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol 2009, 19, 207–212.
  • Mehler MF. Epigenetic principles and mechanisms underlying nervous system functions in health and disease. Prog Neurobiol 2008, 86, 305–341.
  • Bird A. Perceptions of epigenetics. Nature 2007, 447, 396–398.
  • Mattick JS. Deconstructing the dogma: a new view of the evolution and genetic programming of complex organisms. Ann N Y Acad Sci 2009, 1178, 29–46.
  • Mehler MF, Mattick JS. Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol Rev 2007, 87, 799–823.
  • Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci 2004, 7, 847–854.
  • Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005, 308, 1466–1469.
  • Alberini CM. Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 2009, 89, 121–145.
  • Penner MR, Roth TL, Barnes CA, Sweatt JD. An epigenetic hypothesis of aging-related cognitive dysfunction. Front Aging Neurosci 2010, 2, 9.
  • Takei S, Morinobu S, Yamamoto S, Fuchikami M, Matsumoto T, Yamawaki S. Enhanced hippocampal BDNF/TrkB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder. J Psychiatr Res 2011, 45, 460–468.
  • Kang J, Shi Y, Xiang B, Qu B, Su W, Zhu M, Zhang M, Bao G, Wang F, Zhang X, Yang R, Fan F, Chen X, Pei G, Ma L. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell 2005, 123, 833–847.
  • Chiechio S, Zammataro M, Morales ME, Busceti CL, Drago F, Gereau RW 4th, Copani A, Nicoletti F. Epigenetic modulation of mGlu2 receptors by histone deacetylase inhibitors in the treatment of inflammatory pain. Mol Pharmacol 2009, 75, 1014–1020.
  • Vetencourt JF, Tiraboschi E, Spolidoro M, Castrén E, Maffei L. Serotonin triggers a transient epigenetic mechanism that reinstates adult visual cortex plasticity in rats. Eur J Neurosci 2011, 33, 49–57.
  • Sun W, Yang J. Molecular basis of lysophosphatidic acid-induced NF-κB activation. Cell Signal 2010, 22, 1799–1803.
  • Wang HH, Hsieh HL, Yang CM. Nitric oxide production by endothelin-1 enhances astrocytic migration via the tyrosine nitration of matrix metalloproteinase-9. J Cell Physiol 2010.
  • Mitra AK, Gao L, Zucker IH. Angiotensin II-induced upregulation of AT(1) receptor expression: sequential activation of NF-κB and Elk-1 in neurons. Am J Physiol. Cell Physiol 2010, 299, C561–C569.
  • Pizzi M, Sarnico I, Boroni F, Benarese M, Steimberg N, Mazzoleni G, Dietz GP, Bahr M, Liou HC, Spano PF. NF-κB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity. Cell Death Differ 2005, 102, 8752–8757.
  • O’Riordan KJ, Huang IC, Pizzi M, Spano P, Boroni F, Egli R, Desai P, Fitch O, Malone L, Ahn HJ, Liou HC, Sweatt JD, Levenson JM. Regulation of nuclear factor kappaB in the hippocampus by group I metabotropic glutamate receptors. J Neurosci 2006, 26, 4870–4879.
  • Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L. SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-κB signaling. J Biol Chem 2005, 280, 40364–40374.
  • Pizzi M, Spano P. Distinct roles of diverse nuclear factor-kappaB complexes in neuropathological mechanisms. Eur J Pharmacol 2006, 545, 22–28.
  • Chen LF, Williams SA, Mu Y, Nakano H, Duerr JM, Buckbinder L, Greene WC. NF-κB RelA phosphorylation regulates RelA acetylation. Mol Cell Biol 2005, 25, 7966–7975.
  • West AE, Griffith EC, Greenberg ME. Regulation of transcription factors by neuronal activity. Nat Rev Neurosci 2002, 3, 921–931.
  • Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D. NF-κB functions in synaptic signaling and behavior. Nat Neurosci 2003, 6, 1072–1078.
  • Blondeau N, Widmann C, Lazdunski M, Heurteaux C. Activation of the nuclear factor-kappaB is a key event in brain tolerance. J Neurosci 2001, 21, 4668–4677.
  • Grilli M, Pizzi M, Memo M, Spano P. Neuroprotection by aspirin and sodium salicylate through blockade of NF-κB activation. Science 1996, 274, 1383–1385.
  • Pizzi M, Goffi F, Boroni F, Benarese M, Perkins SE, Liou HC, Spano P. Opposing roles for NF-κB/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1beta. J Biol Chem 2002, 277, 20717–20723.
  • Valerio A, Boroni F, Benarese M, Sarnico I, Ghisi V, Bresciani LG, Ferrario M, Borsani G, Spano P, Pizzi M. NF-κB pathway: a target for preventing beta-amyloid (Abeta)-induced neuronal damage and Abeta42 production. Eur J Neurosci 2006, 23, 1711–1720.
  • Inta I, Paxian S, Maegele I, Zhang W, Pizzi M, Spano P, Sarnico I, Muhammad S, Herrmann O, Inta D, Baumann B, Liou HC, Schmid RM, Schwaninger M. Bim and Noxa are candidates to mediate the deleterious effect of the NF-κB subunit RelA in cerebral ischemia. J Neurosci 2006, 26, 12896–12903.
  • Sarnico I, Lanzillotta A, Boroni F, Benarese M, Alghisi M, Schwaninger M, Inta I, Battistin L, Spano P, Pizzi M. NF-κB p50/RelA and c-Rel-containing dimers: opposite regulators of neuron vulnerability to ischaemia. J Neurochem 2009, 108, 475–485.
  • Chen LF, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB. EMBO J 2002, 21, 6539–6548.
  • Kiernan R, Brès V, Ng RW, Coudart MP, El Messaoudi S, Sardet C, Jin DY, Emiliani S, Benkirane M. Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65. J Biol Chem 2003, 278, 2758–2766.
  • Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004, 23, 2369–2380.
  • Lanzillotta A, Sarnico I, Ingrassia R, Boroni F, Branca C, Benarese M, Faraco G, Blasi F, Chiarugi A, Spano P, Pizzi M. The acetylation of RelA in Lys310 dictates the NF-κB dependent response in post-ischemic injury. Cell Death Dis 2010, 1, e96.
  • Christopoulos A, Kenakin T. G protein-coupled receptor allosterism and complexing. Pharmacol Rev 2002, 54, 323–374.
  • Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest 2002, 110, 597–603.
  • Hemler ME. Targeting of tetraspanin proteins–potential benefits and strategies. Nat Rev Drug Discov 2008, 7, 747–758.
  • Martin F, Roth DM, Jans DA, Pouton CW, Partridge LJ, Monk PN, Moseley GW. Tetraspanins in viral infections: a fundamental role in viral biology? J Virol 2005, 79, 10839–10851.
  • Wakabayashi T, Craessaerts K, Bammens L, Bentahir M, Borgions F, Herdewijn P, Staes A, Timmerman E, Vandekerckhove J, Rubinstein E, Boucheix C, Gevaert K, De Strooper B. Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains. Nat Cell Biol 2009, 11, 1340–1346.
  • Isalan M, Lemerle C, Michalodimitrakis K, Horn C, Beltrao P, Raineri E, Garriga-Canut M, Serrano L. Evolvability and hierarchy in rewired bacterial gene networks. Nature 2008, 452, 840–845.
  • Muotri AR, Gage FH. Generation of neuronal variability and complexity. Nature 2006, 441, 1087–1093.
  • Chan SL, Cui Y, van Hasselt A, Li H, Srivastava G, Jin H, Ng KM, Wang Y, Lee KY, Tsao GS, Zhong S, Robertson KD, Rha SY, Chan AT, Tao Q. The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. Lab Invest 2007, 87, 644–650.
  • Fischer JR, Ohnmacht U, Rieger N, Zemaitis M, Stoffregen C, Manegold C, Lahm H. Prognostic significance of RASSF1A promoter methylation on survival of non-small cell lung cancer patients treated with gemcitabine. Lung Cancer 2007, 56, 115–123.
  • Lesniak W, Slomnicki LP, Kuznicki J. Epigenetic control of the S100A6 (calcyclin) gene expression. J Invest Dermatol 2007, 127, 2307–2314.
  • Mattick JS, Mehler MF. RNA editing, DNA recoding and the evolution of human cognition. Trends Neurosci 2008, 31, 227–233.
  • St Laurent G 3rd, Wahlestedt C. Noncoding RNAs: couplers of analog and digital information in nervous system function? Trends Neurosci 2007, 30, 612–621.
  • Bhindi R, Fahmy RG, Lowe HC, Chesterman CN, Dass CR, Cairns MJ, Saravolac EG, Sun LQ, Khachigian LM. Brothers in arms: DNA enzymes, short interfering RNA, and the emerging wave of small-molecule nucleic acid-based gene-silencing strategies. Am J Pathol 2007, 171, 1079–1088.
  • Ptak C, Petronis A. Epigenetics and complex disease: from etiology to new therapeutics. Annu Rev Pharmacol Toxicol 2008, 48, 257–276.
  • Wood M, Yin H, McClorey G. Modulating the expression of disease genes with RNA-based therapy. PLoS Genet 2007, 3, e109.
  • Woolf PJ, Linderman JJ. Self organization of membrane proteins via dimerization. Biophys Chem 2003, 104, 217–227.
  • Kofahl B, Klipp E. Modelling the dynamics of the yeast pheromone pathway. Yeast 2004, 21, 831–850.
  • Guidolin D, Ciruela F, Genedani S, Guescini M, Tortorella C, Albertin G, Fuxe K, Agnati LF. Bioinformatics and mathematical modelling in the study of receptor-receptor interactions and receptor oligomerization. Focus on adenosine receptors. Biochim Biophys Acta 2010 doi:10.1016/j.bbamem.2010.09.022.
  • Rovira X, Roche D, Serra J, Kniazeff J, Pin JP, Giraldo J. Modeling the binding and function of metabotropic glutamate receptors. J Pharmacol Exp Ther 2008, 325, 443–456.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.