The role of dopamine receptor dimer complexes in the pathogenesis of depression

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

This abstract discusses the oligomerization of G protein-coupled receptors (GPCRs), which significantly expands the functional capabilities of cells in living organisms by modulating intracellular signaling pathways. This provides a variety of physiological effects in both normal and pathological states. The structure and localization in the brain of one of the most studied heterodimers, the D1-D2 receptor complex, and its signaling cascades, which correlate with the development of depressive disorders, are examined. Sexual differences in the functioning of this heterodimer are analyzed, and the issue of the selectivity of bivalent synthetic ligands in activating specific intracellular pathways is discussed, highlighting their potential as therapeutic targets for the targeted treatment of depressive disorders. The concluding part of the abstract addresses the diversity of dopamine receptor heterodimers with other members of the GPCR family and their role in the pathophysiology of depression.

About the authors

А. А. Gerasimov

Lomonosov Moscow State University

Author for correspondence.
Email: drewgerasimov@gmail.com
Russian Federation, Moscow

О. V. Smirnova

Lomonosov Moscow State University

Email: drewgerasimov@gmail.com
Russian Federation, Moscow

References

  1. Kaur S, Singh S, Jaiswal G, Kumar S, Hourani W, Gorain B, Kumar P (2020) Pharmacology of Dopamine and Its Receptors. Front Pharmacol Neurotransmit: 143–182. https://doi.org/10.1007/978-981-15-3556-7_5
  2. Misganaw D (2021) Heteromerization of dopaminergic receptors in the brain: Pharmacological implications. Pharmacol Res 170: 105600. https://doi.org/10.1016/j.phrs.2021.105600
  3. Perreault ML, Hasbi A, O’Dowd BF, George SR (2014) Heteromeric Dopamine Receptor Signaling Complexes: Emerging Neurobiology and Disease Relevance. Neuropsychopharmacology 39: 156–168. https://doi.org/10.1038/npp.2013.148
  4. Lubomski M, Davis RL, Sue CM (2020) Depression in Parkinson’s disease: Perspectives from an Australian cohort. J Affect Disord 277: 1038–1044. https://doi.org/10.1016/j.jad.2020.09.032
  5. Dean J, Keshavan M (2017) The neurobiology of depression: An integrated view. Asian J Psychiatry 27: 101–111. https://doi.org/10.1016/j.ajp.2017.01.025
  6. Szczypiński JJ, Gola M (2018) Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia? Rev Neurosci 29: 727–744. https://doi.org/10.1515/revneuro-2017-0091
  7. Maggio R, Aloisi G, Silvano E, Rossi M, Millan MJ (2009) Heterodimerization of dopamine receptors: new insights into functional and therapeutic significance. Parkinsonism Relat Disord 15: S2–S7. https://doi.org/10.1016/S1353-8020(09)70826-0
  8. George SR, Kern A, Smith RG, Franco R (2014) Dopamine receptor heteromeric complexes and their emerging functions. Progr Вrain Res 211: 183–200. https://doi.org/10.1016/B978-0-444-63425-2.00008-8
  9. Johnson GP, Agwuegbo U, Jonas KC (2021) New insights into the functional impact of G protein–coupled receptor oligomerization. Curr Opin Endocr Metab Res 16: 43–50. https://doi.org/10.1016/j.coemr.2020.08.005
  10. Ferré S, Ciruela F, Casadó V, Pardo L (2020) Oligomerization of G protein-coupled receptors: Still doubted? Progr Mol Biol Translat Sci 169: 297–321. https://doi.org/10.1016/bs.pmbts.2019.11.006
  11. Hu S, Wang D, Liu W, Wang Y, Chen J, Cai X (2024) Apelin receptor dimer: Classification, future prospects, and pathophysiological perspectives. Biochim Biophys Acta BBA – Mol Basis Dis 1870: 167257. https://doi.org/10.1016/j.bbadis.2024.167257
  12. Shah U, Pincas H, Sealfon SC, González-Maeso J (2020) Structure and function of serotonin GPCR heteromers. Handbook Behav Neurosci 31: 217–238. https://doi.org/10.1016/B978-0-444-64125-0.00011-6
  13. Yeganeh-Hajahmadi M, Moosavi-Saeed Y, Rostamzadeh F (2023) Apelin Receptor Dimerization and Oligomerization. Curr Mol Pharmacol 17: e180823219999. https://doi.org/10.2174/1874467217666230818113538
  14. Gahbauer S, Böckmann RA (2020) Comprehensive Characterization of Lipid-Guided G Protein-Coupled Receptor Dimerization. J Phys Chem B 124: 2823–2834. https://doi.org/10.1021/acs.jpcb.0c00062
  15. Mirchandani-Duque M, Choucri M, Hernández-Mondragón JC, Crespo-Ramírez M, Pérez-Olives C, Ferraro L, Franco R, Pérez De La Mora M, Fuxe K, Borroto-Escuela DO (2024) Membrane Heteroreceptor Complexes as Second-Order Protein Modulators: A Novel Integrative Mechanism through Allosteric Receptor – Receptor Interactions. Membranes 14: 96. https://doi.org/10.3390/membranes14050096
  16. Faron-Górecka A, Szlachta M, Kolasa M, Solich J, Górecki A, Kuśmider M, Żurawek D, Dziedzicka-Wasylewska M (2019) Understanding GPCR dimerization. Methods Cell Biol 149: 155–178. https://doi.org/10.1016/bs.mcb.2018.08.005
  17. Johnstone EKM, See HB, Abhayawardana RS, Song A, Rosengren KJ, Hill SJ, Pfleger KDG (2021) Investigation of Receptor Heteromers Using NanoBRET Ligand Binding. Int J Mol Sci 22: 1082. https://doi.org/10.3390/ijms22031082
  18. Dale NC, Johnstone EKM, Pfleger KDG (2022) GPCR heteromers: An overview of their classification, function and physiological relevance. Front Endocrinol 13: 931573. https://doi.org/10.3389/fendo.2022.931573
  19. Odagaki Y, Borroto-Escuela DO (2019) Co-Immunoprecipitation Methods for Brain Tissue. Humana Press. https://doi.org/10.1007/978-1-4939-8985-0
  20. Lujan R, Ciruela F (2021) Receptor and Ion Channel Detection in the Brain. Humana Press. https://doi.org/10.1007/978-1-0716-1522-5
  21. Guo H, An S, Ward R, Yang Y, Liu Y, Guo X-X, Hao Q, Xu T-R (2017) Methods used to study the oligomeric structure of G-protein-coupled receptors. Biosci Rep 37: BSR20160547. https://doi.org/10.1042/BSR20160547
  22. Zhao F, Cheng Z, Piao J, Cui R, Li B (2022) Dopamine Receptors: Is It Possible to Become a Therapeutic Target for Depression? Front Pharmacol 13: 947785. https://doi.org/10.3389/fphar.2022.947785
  23. Vekshina NL, Anokhin PK, Veretinskaya AG, Shamakina IYu (2017) Heterodimeric D1-D2 dopamine receptors: a review. Biomed Khimiya 63: 5–12. https://doi.org/10.18097/PBMC20176301005
  24. Beaulieu J-M, Gainetdinov RR (2011) The Physiology, Signaling, and Pharmacology of Dopamine Receptors. Pharmacol Rev 63: 182–217. https://doi.org/10.1124/pr.110.002642
  25. Iwakura Y, Nawa H, Sora I, Chao MV (2008) Dopamine D1 Receptor-induced Signaling through TrkB Receptors in Striatal Neurons. J Biol Chem 283: 15799–15806. https://doi.org/10.1074/jbc.M801553200
  26. Juza R, Musilek K, Mezeiova E, Soukup O, Korabecny J (2023) Recent advances in dopamine D2 receptor ligands in the treatment of neuropsychiatric disorders. Med Res Rev 43: 55–211. https://doi.org/10.1002/med.21923
  27. Beaulieu J-M, Tirotta E, Sotnikova TD, Masri B, Salahpour A, Gainetdinov RR, Borrelli E, Caron MG (2007) Regulation of Akt Signaling by D2 and D3 Dopamine Receptors In Vivo. J Neurosci 27: 881–885. https://doi.org/10.1523/JNEUROSCI.5074-06.2007
  28. Delva NC, Stanwood GD (2021) Dysregulation of brain dopamine systems in major depressive disorder. Exp Biol Med 246: 1084–1093. https://doi.org/10.1177/1535370221991830
  29. Kim H, Nam M-H, Jeong S, Lee H, Oh S-J, Kim J, Choi N, Seong J (2022) Visualization of differential GPCR crosstalk in DRD1-DRD2 heterodimer upon different dopamine levels. Prog Neurobiol 213: 102266. https://doi.org/10.1016/j.pneurobio.2022.102266
  30. O’Dowd BF, Ji X, Nguyen T, George SR (2012) Two amino acids in each of D1 and D2 dopamine receptor cytoplasmic regions are involved in D1–D2 heteromer formation. Biochem Biophys Res Commun 417: 23–28. https://doi.org/10.1016/j.bbrc.2011.11.027
  31. Hasbi A, O’Dowd BF, George SR (2011) Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance. Mol Brain 4: 26. https://doi.org/10.1186/1756-6606-4-26
  32. Hasbi A, Nguyen T, Rahal H, Manduca JD, Miksys S, Tyndale RF, Madras BK, Perreault ML, George SR (2020) Sex difference in dopamine D1-D2 receptor complex expression and signaling affects depression- and anxiety-like behaviors. Biol Sex Differ 11: 8. https://doi.org/10.1186/s13293-020-00285-9
  33. Hasbi A, Fan T, Alijaniaram M, Nguyen T, Perreault ML, O’Dowd BF, George SR (2009) Calcium signaling cascade links dopamine D1–D2 receptor heteromer to striatal BDNF production and neuronal growth. Proc Natl Acad Sci U S A 106: 21377–21382. https://doi.org/10.1073/pnas.0903676106
  34. Joormann J, Gotlib IH (2010) Emotion regulation in depression: Relation to cognitive inhibition. Cogn Emot 24: 281–298. https://doi.org/10.1080/02699930903407948
  35. Фонсова НА, Сергеев ИЮ, Дубынин ВА (2016) Анатомия центральной нервной системы. Учебник для академического бакалавриата. М.; Изд-во Юрайт. [Fonsova NA, Sergeev IYU, Dubynin VA (2016) Anatomy of the Central Nervous System. A Textbook for Academic Bachelor's Degree. M. YUrajt. (In Russ)].
  36. Koo JW, Chaudhury D, Han M-H, Nestler EJ (2019) Role of Mesolimbic Brain-Derived Neurotrophic Factor in Depression. Biol Psychiatry 86: 738–748. https://doi.org/10.1016/j.biopsych.2019.05.020
  37. Fatima M, Ahmad MH, Srivastav S, Rizvi MA, Mondal AC (2020) A selective D2 dopamine receptor agonist alleviates depression through up-regulation of tyrosine hydroxylase and increased neurogenesis in hippocampus of the prenatally stressed rats. Neurochem Int 136: 104730. https://doi.org/10.1016/j.neuint.2020.104730
  38. Strickland JA, Austen JM, Sprengel R, Sanderson DJ (2021) The GluA1 AMPAR subunit is necessary for hedonic responding but not hedonic value in female mice. Physiol Behav 228: 113206. https://doi.org/10.1016/j.physbeh.2020.113206
  39. Dolgacheva LP, Tuleukhanov ST, Zinchenko VP (2020) Participation of Ca2+-Permeable AMPA Receptors in Synaptic Plasticity. Biochemistry (Moscow) Suppl Ser A: Membrane And Cell Biology 37: 175–187. https://doi.org/10.31857/S0233475520030044
  40. Shen MYF (2015) The role of the dopamine D1-D2 receptor heteromer in brain reward function: Relevance to drug addiction and depression. Univer Toronto. 1–223.
  41. Phillips C (2017) Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection. Neural Plast 2017: 1–17. https://doi.org/10.1155/2017/7260130
  42. Noori M, Hasbi A, Sivasubramanian M, Milenkovic M, George SR (2020) Maternal Separation Model of Postpartum Depression: Potential Role for Nucleus Accumbens Dopamine D1–D2 Receptor Heteromer. Neurochem Res 45: 2978–2990. https://doi.org/10.1007/s11064-020-03145-5
  43. Pei L, Li S, Wang M, Diwan M, Anisman H, Fletcher PJ, Nobrega JN, Liu F (2010) Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects. Nat Med 16: 1393–1395. https://doi.org/10.1038/nm.2263
  44. Dziedzicka-Wasylewska M, Polit A, Błasiak E, Faron-Górecka A (2024) G Protein-Coupled Receptor Dimerization – What Next? Int J Mol Sci 25: 3089. https://doi.org/10.3390/ijms25063089
  45. Botta J, Appelhans J, McCormick PJ (2020) Continuing challenges in targeting oligomeric GPCR-based drugs. Progr Mol Biol Translat Sci 169: 213–245. https://doi.org/10.1016/bs.pmbts.2019.11.009
  46. Zhuang Y, Xu P, Mao C, Wang L, Krumm B, Zhou XE, Huang S, Liu H, Cheng X, Huang X-P, Shen D-D, Xu T, Liu Y-F, Wang Y, Guo J, Jiang Y, Jiang H, Melcher K, Roth BL, Zhang Y, Zhang C, Xu HE (2021) Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell 184: 931–942.e18. https://doi.org/10.1016/j.cell.2021.01.027
  47. Hasbi A, Madras BK, George SR (2023) Daily Δ9-Tetrahydrocannabinol and Withdrawal Increase Dopamine D1-D2 Receptor Heteromer to Mediate Anhedonia- and Anxiogenic-like Behavior Through a Dynorphin and Kappa Opioid Receptor Mechanism. Biol Psychiatry Glob Open Sci 3: 550–566. https://doi.org/10.1016/j.bpsgos.2022.07.003
  48. Wouters E, Marín A, Dalton J, Giraldo J, Stove C (2019) Distinct Dopamine D2 Receptor Antagonists Differentially Impact D2 Receptor Oligomerization. Int J Mol Sci 20: 1686. https://doi.org/10.3390/ijms20071686
  49. Williams OOF, Coppolino M, George SR, Perreault ML (2021) Sex Differences in Dopamine Receptors and Relevance to Neuropsychiatric Disorders. Brain Sci 11: 1199. https://doi.org/10.3390/brainsci11091199
  50. Shen MYF, Perreault ML, Bambico FR, Jones-Tabah J, Cheung M, Fan T, Nobrega JN, George SR (2015) Rapid anti-depressant and anxiolytic actions following dopamine D1–D2 receptor heteromer inactivation. Eur Neuropsychopharmacol 25: 2437–2448. https://doi.org/10.1016/j.euroneuro.2015.09.004
  51. Mitroshina EV, Marasanova EA, Vedunova MV (2023) Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders. Int J Mol Sci 24: 16416. https://doi.org/10.3390/ijms242216416
  52. Shioda N, Imai Y, Yabuki Y, Sugimoto W, Yamaguchi K, Wang Y, Hikida T, Sasaoka T, Mieda M, Fukunaga K (2019) Dopamine D2L Receptor Deficiency Causes Stress Vulnerability through 5-HT1A Receptor Dysfunction in Serotonergic Neurons. J Neurosci 39: 7551–7563. https://doi.org/10.1523/JNEUROSCI.0079-19.2019
  53. Li W, Ali T, Mou S, Gong Q, Li N, Hao L, Yu Z-J, Li S (2023) D1R-5-HT2AR Uncoupling Reduces Depressive Behaviours via HDAC Signalling. Neurotherapeutics 20: 1875–1892. https://doi.org/10.1007/s13311-023-01436-7
  54. Gonçalves MCB, Glaser T, Oliveira SLBD, Ulrich H (2020) Adenosinergic-Dopaminergic Signaling in Mood Disorders: A Mini-Review. J Caffeine Adenosine Res 10: 94–103. https://doi.org/10.1089/caff.2020.0009
  55. Ferré S, Bonaventura J, Zhu W, Hatcher-Solis C, Taura J, Quiroz C, Cai N-S, Moreno E, Casadó-Anguera V, Kravitz AV, Thompson KR, Tomasi DG, Navarro G, Cordomí A, Pardo L, Lluís C, Dessauer CW, Volkow ND, Casadó V, Ciruela F, Logothetis DE, Zwilling D (2018) Essential Control of the Function of the Striatopallidal Neuron by Pre-coupled Complexes of Adenosine A2A-Dopamine D2 Receptor Heterotetramers and Adenylyl Cyclase. Front Pharmacol 9: 243. https://doi.org/10.3389/fphar.2018.00243
  56. Durdagi S, Erol I, Salmas RE, Aksoydan B, Kantarcioglu I (2019) Oligomerization and cooperativity in GPCRs from the perspective of the angiotensin AT1 and dopamine D2 receptors. Neurosci Lett 700: 30–37. https://doi.org/10.1016/j.neulet.2018.04.028
  57. Amato S, Averna M, Guidolin D, Ceccoli C, Gatta E, Candiani S, Pedrazzi M, Capraro M, Maura G, Agnati LF, Cervetto C, Marcoli M (2023) Heteromerization of Dopamine D2 and Oxytocin Receptor in Adult Striatal Astrocytes. Int J Mol Sci 24: 4677. https://doi.org/10.3390/ijms24054677
  58. Cervetto C, Maura G, Guidolin D, Amato S, Ceccoli C, Agnati LF, Marcoli M (2023) Striatal astrocytic A2A-D2 receptor-receptor interactions and their role in neuropsychiatric disorders. Neuropharmacology 237: 109636. https://doi.org/10.1016/j.neuropharm.2023.109636

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Russian Academy of Sciences