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Vol. 85, No. 3, 2007
Issue release date: June 2007
Neuroendocrinology 2007;85:186–192
(DOI:10.1159/000101917)

Dynamics of Glucocorticoid Receptor and Mineralocorticoid Receptor: Implications from Live Cell Imaging Studies

Nishi M. · Kawata M.
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan

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Abstract

Adrenal corticosteroids (cortisol in humans/corticosterone in rodents) readily enter the brain and exert markedly diverse effects, such as the stress response of target neural cells. These effects are regulated via two receptor systems, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), both of which are ligand-inducible transcription factors. It is generally accepted that GR and MR predominantly reside in the cytoplasm in the absence of corticosterone (CORT), and are quickly translocated into the nucleus upon binding CORT. Then these receptors form dimers to bind hormone-responsive elements and regulate the expression of target genes. Given the different actions of MR and GR in the central nervous system, it is important to elucidate how the trafficking of these receptors between the cytoplasm and nucleus and their interaction are regulated by ligands or other molecules to exert transcriptional activity. However, the precise mechanisms of these processes are still not completely clarified. To address these issues, we have tried to observe more dynamic subcellular trafficking processes in living cells by employing a green fluorescent protein. In this review, we describe our recent studies of corticosteroid receptor dynamics in living cells focusing on three points: (1) the effects of a ligand, corticosteroid; (2) the carrier molecules involved in active nuclear transport, importins, and (3) the possibility of heterodimer formation. These studies demonstrate that GR and MR were quickly translocated from the cytoplasm to the nucleus after CORT treatment by associating with importin molecules. GR and MR differed in their response to the concentration of CORT in neural cells and non-neural cells. In the nuclear region, we detected GR-MR heterodimers, which were affected by changes in CORT concentrations in response to various hormonal milieus such as circadian rhythm and stress.



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References

  1. McEwen BS, Weiss JM, Schwartz L: Selective retention of corticosterone by limbic structures in rat brain. Nature 1968;220:911–912.
  2. Arriza JL, Simerly RB, Swanson LW, Evans RM: The neuronal mineralocorticoid receptor as a mediator of glucocorticoid response. Neuron 1988;1:887–900.
  3. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M: Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998;19:269–301.
  4. Rupprecht R, Reul JMHM, van Steensel B, Spengler D, Soder M, Berning B, Holsber F, Damm K: Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol 1993;247:145–154.
  5. Kawata M: Roles of steroid hormones and their receptors in structural organization in the nervous system. Neurosci Res 1995;24:1–46.
  6. Joels M, de Kloet ER: Mineralocorticoid and glucocorticoid receptors in the brain. Implication for ion permeability and transmitter systems. Prog Neurobiol 1994;43:1–36.
  7. DeFranco DB: Functional implications of glucocorticoid receptor trafficking. Ernst Schering Res Found Workshop 2002;40:91–109.
  8. Nishi M, Kawata M: Brain corticosteroid receptor dynamics and trafficking: implications from living cell imaging. Neuroscientist 2006;12:119–133.
  9. Meaney MJ, Diorio J, Francis D, Widdowson J, LaPlante P, Caldji C: Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci 1996;18:49–72.
  10. Herman JP, Cullinan WE: Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci 1997;20:78–84.
  11. Nishi M, Ogawa H, Ito T, Matsuda K, Kawata M: Dynamic changes in subcellular localization of mineralocorticoid receptor in living cells: in comparison with glucocorticoid receptor using dual-color labeling with green fluorescent protein spectral variants. Mol Endocrinol 2001;15:1077–1092.
  12. De Kloet ER, Joels M, Holsboer F: Stress and the brain: from adaptation to disease. Nat Rev Neurosci 2005;6:463–475.
  13. Setou M, Nakagawa T, Seog D-H, Hirokawa N: Kinesin superfamily motor protein KIF 17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 2000;288:1796–1802.
  14. Nishi M, Takenaka N, Morita N, Ito T, Ozawa H, Kawata M: Real-time imaging of glucocorticoid receptor dynamics in living neurons and glial cells in comparison with non-neural cells. Eur J Neurosci 1999;11:1927–1936.
  15. Tyagi RK, Amazit L, Lescop P, Milgrom E, Guiochon-Mantel A: Mechanisms of progesterone receptor export from nuclei: role of nuclear localization signal, nuclear export signal, and ran guanosine triphosphate. Mol Endocrinol 1998;12:1684–1695.
  16. Hager GL, Lim CS, Elbi C, Baumann CT: Trafficking of nuclear receptors in living cells. J Steroid Biochem Mol Biol 2000;74:249–254.
  17. Davis LI: The nuclear pore complex. Annu Rev Biochem 1995;64:865–896.
  18. Weis K: Nucleocytoplasmic transport: cargo trafficking across the border. Curr Opin Cell Biol 2002;14:328–335.
  19. Otis KO, Thompson KR, Martin KC: Importin-mediated nuclear transport in neurons. Curr Opin Neurobiol 2006;16:1–7.
  20. Tanaka M, Nishi M, Morimoto M, Kawata M: Nuclear import of glucocorticoid receptor in association with importin α and importin β: analysis with real-time fluorescence imaging and fluorescence resonance energy transfer in living cells. Endocrinology 2003;144:4070–4079.
  21. Power RF, Conneely OM, O’Malley BW: New insights into activation of the steroid hormone receptor superfamily. Trends Pharmacol Sci 1992;13:318–323.
  22. Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM: Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signaling. Nature 1992;355:446–449.
  23. Forman BM, Umesono K, Chen J, Evans RM: Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell 1995;81:541–550.
  24. Liu W, Wang J, Sauter NK, Pearce D: Steroid receptor heterodimerization demonstrated in vitro and in vivo. Proc Natl Acad Sci USA 1995;92:12480–12484.
  25. Lansford R, Bearman G, Fraser SE: Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy. J Biomed Opt 2001;6:311–318.
  26. Nishi M, Tanaka M, Matsuda K, Sunaguchi M, Kawata M: Visualization of glucocorticoid receptor and mineralocorticoid receptor interactions in living cells with GFP-based fluorescence resonance energy transfer. J Neurosci 2004;24:4918–4927.
  27. Miyawaki A: Innovations in the imaging of brain functions using fluorescent proteins. Neuron 2005;48:189–199.
  28. Van Steensel B, van Binnendijk EP, Hornsby C, van der Voort TM, Krozowski ZS, de Kloet ER; and others: Partial colocalization of glucocorticoid and mineralocorticoid receptors in discrete compartments in nuclei of rat hippocampal neurons. J Cell Sci 1996;109:787–792.
  29. De Kloet ER, Rots NY, Desiree TWM, van den Berg M, Oitzl MS: Brain mineralocorticoid receptor function. Ann NY Acad Sci 1994;746:8–21.
  30. Trapp T, Holsber F: Heterodimerization between mineralocorticoid and glucocorticoid receptors increases the functional diversity of corticosteroid action. Trends Pharmacol Sci 1996;17:145–149.
  31. Trapp T, Rupprecht R, Castren M, Reul JMHM, Holsber F: Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS. Neuron 1994;13:1457–1462.
  32. Liu W, Wang J, Sauter NK, Pearce D: Steroid receptor heterodimerization demonstrated in vitro and in vivo. Proc Natl Acad Sci USA 1995;92:12480–12484.
  33. Ou XM, Storring JM, Kushwaha N, Albert PR: Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene. J Biol Chem 2001;276:14299–14307.


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