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Dopaminergic intracellular signal integrating proteins: relevance to schizophrenia

By Bruno R. Souza, Renan P. Souza, Daniela V. F. Rosa, Melissa M. Guirnarães, Humberto Correa and Marco A. Romano-Silva


Changes in dopaminergic function can be regulated by receptor-receptor interaction, or interaction with other proteins with dopamine receptors, and/or elements of the downstream signaling cascades. The complexity of dopaminergic signaling is far from being completely elucidated. It could, however, hold the key to the comprehension of the pathophysiology of neurological and psychiatric disorders, as well as to the identification of putative new targets for, and development of, more efficacious and selective drugs. Here, we review some of the current evidence and new ideas that are being proposed as a result, as well as future perspectives that are now being recognized

Topics: Basic Research
Publisher: Les Laboratoires Servier
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Provided by: PubMed Central

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  1. (1996). A molecular mechanism for the effect of lithium on development.
  2. a novel protein phosphatase 1 binding protein localized to dendritic spines.
  3. (1991). A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science.
  4. Abnormalities in the dopamine system in schizophrenia may lie in altered levels of dopamine receptor-interacting proteins. Biol Psychiatry.
  5. Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Mol Pharmacol.
  6. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior.
  7. Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia.
  8. (2002). Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet.
  9. Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280). Biochem Pharmacol.
  10. Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein.
  11. Bidirectional regulation of DARPP-32 phosphorylation by dopamine.
  12. (2001). Ca2+ elevation evoked by membrane depolarization regulates G protein cycle via RGS proteins in the heart. Circ Res.
  13. Ca2+/calmodulin reverses phosphatidylinositol 3,4,5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity.
  14. Calcium signaling dysfunction in schizophrenia: a unifying approach.
  15. Cell signal control of the G protein-gated potassium channel and its subcellular localization.
  16. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors.
  17. Confirming RGS4 as a susceptibility gene for schizophrenia.
  18. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia.
  19. (2005). D'Mello SR. Inhibition of GSK3beta is a common event in neuroprotection by different survival factors. Brain Res Mol Brain Res.
  20. D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor.
  21. D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade.
  22. (2001). Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry.
  23. (2004). Dopamine D1 and D2 receptor co-activation generates a novel phospholipase C-mediated calcium signal. J Biol Chem.
  24. Dopamine receptor nteracting proteins: the Ca(2+) connection in dopamine signaling. Trends Pharmacol Sci.
  25. Dopamine receptor oligomerization visualized in living cells.
  26. Dopamine receptor signaling.
  27. Dopamine receptor-mediated regulation of RGS2 and RGS4 mRNA differentially depends on ascending dopamine projections and time.
  28. Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin.
  29. (1995). Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder.
  30. Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia. Arch Gen Psychiatry.
  31. (2005). Existence and theoretical aspects of homomeric and heteromeric dopamine receptor complexes and their relevance for neurological diseases. Neuromolecular Med.
  32. Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians.
  33. (2002). G-protein-coupled receptor oligomerization and its potential for drug discovery. Nat Rev Drug Discov.
  34. Generation and characterization of Rgs4 mutant mice.
  35. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II:
  36. GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling.
  37. (2002). Glycogen synthase kinase-3 inhibition by lithium and beryllium suggests the presence of two magnesium binding sites. Biochem Biophys Res Commun.
  38. Glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal cortex in schizophrenia.
  39. (2004). GSK-3 parameters in postmortem frontal cortex and hippocampus of schizophrenic patients. Schizophr Res.
  40. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen.
  41. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase
  42. Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor.
  43. Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors.
  44. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade.
  45. (1996). Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol.
  46. (2001). Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun.
  47. (2001). Low GSK-3 activity in frontal cortex of schizophrenic patients. Schizophr Res.
  48. Low GSK-3beta immunoreactivity in postmortem frontal cortex of schizophrenic patients.
  49. Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280). Mol Pharmacol.
  50. Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families.
  51. Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily.
  52. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma.
  53. Par-4 links dopamine signaling and depression.
  54. Phosphatidylinositol 3,4,5-trisphosphate and Ca2+/calmodulin competitively bind to the regulators of G-protein-signalling (RGS) domain of RGS4 and reciprocally regulate its action.
  55. Physiological actions of regulators of G-protein signaling (RGS). Proteins Life Sci.
  56. PIP3 inhibition of RGS protein and its reversal by Ca2+/calmodulin mediate voltage-dependent control of the G protein cycle in a cardiac K+ channel.
  57. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction.
  58. Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines.
  59. (1998). Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations.
  60. Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors.
  61. Striatal gene expression of RGS2 and RGS4 is specifically mediated by dopamine D1 and D2 receptors: clues for RGS2 and RGS4 functions.
  62. Subcellular localization of the dopamine D2 receptor and coexistence with the calcium-binding protein neuronal calcium sensor-1 in the primate prefrontal cortex.
  63. (2004). Support for RGS4 as a susceptibility gene for schizophrenia. Biol Psychiatry.
  64. The protein kinase B/Akt signalling pathway in human malignancy.
  65. (1995). The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
  66. The role of calmodulin as a signal integrator for synaptic plasticity. Nat Rev Neurosci.
  67. Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia. Arch Gen Psychiatry.
  68. Upregulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients.