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Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: Implications for major depressive disorder
Open accessAbstract
Mood disorders associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis are common psychiatric conditions. The glucocorticoid receptor (GR) is a steroid-activated nuclear receptor that, upon binding to cortisol, translocates to the nucleus where it targets genes related to neuronal metabolism and plasticity. In patients suffering from major depressive disorder (MDD), hypercortisolemia is a common finding. In the current study we investigated the molecular events associated with the FK506 binding proteins (FKBP) -52 and -51 response to cortisol exposure in neuronal cell cultures and their effect on GR translocation. We noted that FK506 altered nuclear localization of the GR and inhibited expression of GR-responsive genes. Furthermore, si-RNA knockdown of FKBP4 gene, coding for the immunophilin FKBP52, inhibited cortisol-activated GR nuclear translocation, while knockdown of FKBP5, coding for immunophilin FKBP51, was associated with increased baseline GR nuclear localization. We propose that immunophilins are modulators of the cortisol-HPA axis response to stress and related chronic brain disorders.
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“FKBP51 inhibits GR ligand binding, nuclear translocation and transcriptional activity, while FKBP52 potentiates each of these fundamental GR activities22–32.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [25]
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“FKBP52 stabilizes ligand-bound GR, resulting in enhanced ligand affinity, and facilitates rapid GR nuclear translocation on dynein22,24,25,65, allowing GR to proceed with dimerization and transcription activation.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [25]
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Cites
Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis
Ozer, E. J., Best, S. R., Lipsey, T. L., & Weiss, D. S. (2003) · Psychological Bulletin · doi:10.1037/0033-2909.129.1.52 · Cited by 3,322 · cited 10×
“In fact, transgenicmice thatunder-orover-express GR have been used asmodels ofMDDor PTSD (Alexandre Urani, 2003;Chourbaji et al., 2008;Gasset al., 2001).”
BackgroundInfluentialThe Neuroendocrinology of Stress and Aging: The Glucocorticoid Cascade Hypothesis
Sapolsky, R. M., Krey, L. C., & McEwen, B. S. (1986) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2002.38.cp21 · Cited by 2,343
Binder, E. B. (2008) · JAMA · doi:10.1001/jama.299.11.1291 · Cited by 1,362
Predictors of posttraumatic stress disorder and symptoms in adults: A meta-analysis.
Ozer, E. J., Best, S. R., Lipsey, T. L., & Weiss, D. S. (2008) · Psychological Trauma Theory Research Practice and Policy · doi:10.1037/1942-9681.s.1.3 · Cited by 1,252
Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment
Pariante, C. M., & Miller, A. H. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01088-x · Cited by 1,147
Clinical and Biochemical Manifestations of Depression
Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988) · New England Journal of Medicine · doi:10.1056/nejm198808183190706 · Cited by 1,057
Binder, E. B., Salyakina, D., Lichtner, P., Wochnik, G. M., Ising, M., Pütz, B., Papiol, S., Seaman, S., Lucae, S., Kohli, M. A., et al. (2004) · Nature Genetics · doi:10.1038/ng1479 · Cited by 977
DNA binding site sequence directs glucocorticoid receptor structure and activity
Meijsing, S. H., Pufall, M. A., So, A. Y., Bates, D. L., Chen, L., & Yamamoto, K. R. (2009) · Science · doi:10.1126/science.1164265 · Cited by 673
Wochnik, G. M., Rüegg, J., Abel, G. A., Schmidt, U., Holsboer, F., & Rein, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m407498200 · Cited by 638
Påhlman, S., Ruusala, A.-I., Abrahamsson, L., Mattsson, M. E. K., & Esscher, T. (1984) · Cell Differentiation · doi:10.1016/0045-6039(84)90038-1 · Cited by 571
The stress system in depression and neurodegeneration: Focus on the human hypothalamus
Bao, A., Meynen, G., & Swaab, D. F. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.04.005 · Cited by 565
A New First Step in Activation of Steroid Receptors
Davies, T. H., Ning, Y.-M., & Sánchez, E. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100531200 · Cited by 427
Webster, M. J., Knable, M. B., O'Grady, J., Orthmann, J., & Weickert, C. S. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001139 · Cited by 420
Francis, B. (1993) · Datamation · Cited by 365
Polymorphisms of the Glucocorticoid Receptor Gene and Major Depression
van Rossum, E. F. C., Binder, E. B., Majer, M., Koper, J. W., Ising, M., Modell, S., Salyakina, D., Lamberts, S. W. J., & Holsboer, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.007 · Cited by 329
Wang, J.-C., Derynck, M. K., Nonaka, D. F., Khodabakhsh, D. B., Haqq, C., & Yamamoto, K. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407008101 · Cited by 320
Ising, M., Depping, A., Siebertz, A., Lucae, S., Unschuld, P. G., Kloiber, S. M., Horstmann, S., Uhr, M., Müller‐Myhsok, B., & Holsboer, F. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06332.x · Cited by 320
Pathophysiology of hypercortisolism in depression
Carroll, B. J., Cassidy, F., Naftolowitz, D., Tatham, N. E., Wilson, W. H., Iranmanesh, A., Liu, P. Y., & Veldhuis, J. D. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.00967.x · Cited by 317
Loss of Glucocorticoid Fast Feedback in Depression
Young, E. A. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810320017003 · Cited by 299
Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement
Pratt, W. B., Galigniana, M. D., Harrell, J. M., & DeFranco, D. B. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.02.004 · Cited by 285
Opposing roles of type I and type II adrenal steroid receptors in hippocampal long-term potentiation
Pavlides, C., Watanabe, Y., Magarin˜os, A. M., & McEwen, B. S. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00151-8 · Cited by 261
Sinars, C. R., Cheung-Flynn, J., Rimerman, R. A., Scammell, J. G., Smith, D. F., & Clardy, J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0231020100 · Cited by 254
Kohda, K., Harada, K., Kato, K., Hoshino, A., Motohashi, J., Yamaji, T., Morinobu, S., Matsuoka, N., & Kato, N. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.05.041 · Cited by 252
Cochaperone immunophilin FKBP52 is critical to uterine receptivity for embryo implantation
Tranguch, S., Cheung-Flynn, J., Daikoku, T., Prapapanich, V., Cox, M. B., Xie, H., Wang, H., Das, S. K., Smith, D. F., & Dey, S. K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505775102 · Cited by 232
Glucocorticoid and Mineralocorticoid Receptor mRNA Expression in Rat Brain
Chao, H. M., Choo, P. H., & McEwen, B. S. (2008) · Neuroendocrinology · doi:10.1159/000125250 · Cited by 217
HSP56: a novel heat shock protein associated with untransformed steroid receptor complexes
Sanchez, E. R. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45667-0 · Cited by 214
Physiological role for the cochaperone FKBP52 in androgen receptor signaling
Cheung-Flynn, J., Prapapanich, V., Cox, M. B., Riggs, D. L., Suarez-Quian, C., & Smith, D. F. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0071 · Cited by 212
Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids
Hubler, T. R., & Scammell, J. G. (2004) · Cell Stress & Chaperones · doi:10.1379/csc-32r.1 · Cited by 201
Reynolds, P. D., Ruan, Y., Smith, D. F., & Scammell, J. G. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.2.5429 · Cited by 184
Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children
Koenen, K. C., Saxe, G., Purcell, S., Smoller, J. W., Bartholomew, D. A., Miller, A. B., Hall, E., Kaplow, J. B., Enlow, M. B., Moulton, S. L., et al. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001727 · Cited by 182
Davies, T. H., Ning, Y.-M., & Sánchez, E. R. (2005) · Biochemistry · doi:10.1021/bi048503v · Cited by 180
Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms
Chrousos, G. P., Renquist, D., Brandon, D., Eil, C., Pugeat, M., Vigersky, R., Cutler, G. B., Loriaux, D. L., & Lipsett, M. B. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.6.2036 · Cited by 179
Callebaut, I., Renoir, J., Lebeau, M., Massol, N., Burny, A., Baulieu, E. E., & Mornon, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.14.6270 · Cited by 167
Wu, B., Li, P., Liu, Y., Lou, Z., Ding, Y., Shu, C., Ye, S., Bartlam, M., Shen, B., & Rao, Z. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305969101 · Cited by 165
Deroo, B. J., Rentsch, C., Sampath, S., Young, J., DeFranco, D. B., & Archer, T. K. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.12.4113-4123.2002 · Cited by 164
Molecular chaperones function as steroid receptor nuclear mobility factors
Elbi, C., Walker, D. A., Romero, G. G., Sullivan, W. P., Toft, D. O., Hager, G. L., & DeFranco, D. B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400116101 · Cited by 144
Tombaugh, G. C., Yang, S. H., Swanson, R. A., & Sapolsky, R. M. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08884.x · Cited by 137
Evidence for glucocorticoid receptor transport on microtubules by dynein
Harrell, J. M., Murphy, P. J. M., Morishima, Y., Chen, H., Mansfield, J. F., Galigniana, M. D., & Pratt, W. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406863200 · Cited by 129
Gass, P., Reichardt, H. M., Strekalova, T. V., Henn, F. A., & Tronche, F. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00518-2 · Cited by 121
Galigniana, M. D., Harrell, J. M., Murphy, P. J. M., Chinkers, M., Radanyi, C., Renoir, J.-M., Zhang, M., & Pratt, W. B. (2002) · Biochemistry · doi:10.1021/bi020399z · Cited by 117
Zhang, X., Clark, A. F., & Yorio, T. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-1279 · Cited by 116
Pituitary-Adrenal Function in the Squirrel Monkey
Brown, G. M., Grota, L. J., Penney, D. P., & Reichlin, S. (1970) · Endocrinology · doi:10.1210/endo-86-3-519 · Cited by 100
Giraudier, S., Chagraoui, H., Komura, E., Barnache, S., Blanchet, B., Couedic, J. P. L., Smith, D. F., Larbret, F., Taksin, A., Moreau-Gachelin, F., et al. (2002) · Blood · doi:10.1182/blood-2002-02-0485 · Cited by 77
Banerjee, A., Periyasamy, S., Wolf, I. M., Hinds, T. D., Yong, W., Shou, W., & Sanchez, E. R. (2008) · Biochemistry · doi:10.1021/bi8011862 · Cited by 73
BCL-xL Regulates Synaptic Plasticity
Jonas, E. A. (2006) · Molecular Interventions · doi:10.1124/mi.6.4.7 · Cited by 72
Squirrel Monkey Immunophilin FKBP51 Is a Potent Inhibitor of Glucocorticoid Receptor Binding1
Denny, W. B., Valentine, D. L., Reynolds, P. D., Smith, D. F., & Scammell, J. G. (2000) · Endocrinology · doi:10.1210/en.141.11.4107 · Cited by 66
Maccari, S., Mormède, P., Piazza, P., `mon, H., Angelucci, L., & Moal, M. L. (1992) · Psychoneuroendocrinology · doi:10.1016/0306-4530(92)90049-d · Cited by 61
Fitzsimons, C. P., Ahmed, S., Wittevrongel, C. F. W., Schouten, T. G., Dijkmans, T. F., Scheenen, W. J. J. M., Schaaf, M. J. M., de Kloet, E. R., & Vreugdenhil, E. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0233 · Cited by 52
Role of molecular chaperones in subnuclear trafficking of glucocorticoid receptors
DeFranco, D. B. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00957.x · Cited by 50
Lowy, M. T. (2008) · Neuroendocrinology · doi:10.1159/000125336 · Cited by 49
Gawlik, M., Möller-Ehrlich, K., Mende, M., Jovnerovski, M., Jung, S., Jabs, B. E., Knapp, M., & Stoeber, G. (2006) · BMC Psychiatry · doi:10.1186/1471-244x-6-52 · Cited by 45
Wang, X., Pongrac, J. L., & DeFranco, D. B. (2002) · Molecular Endocrinology · doi:10.1210/me.2001-0287 · Cited by 43
Pariante, C. M., Pearce, B. D., Pisell, T. L., Sanchez, C. I., Po, C., Su, C., & Miller, A. H. (1999) · Endocrinology · doi:10.1210/en.140.9.4359 · Cited by 40
The immunosuppressant drug FK506 is a potent trophic agent for human fetal neurons
Avramut, M., Zeevi, A., & Achim, C. L. (2001) · Developmental Brain Research · doi:10.1016/s0165-3806(01)00307-8 · Cited by 38
Self-citationChourbaji, S., Vogt, M. A., & Gass, P. (2007) · Progress in brain research · doi:10.1016/s0079-6123(07)67005-8 · Cited by 32
Neuron-Enriched Second Trimester Human Cultures: Growth Factor Response and in Vivo Graft Survival
White, M. G., Hammond, R. R., Sanders, V. J., Bonaroti, E. A., Mehta, A. P., Wang, G., Wiley, C. A., & Achim, C. L. (1999) · Cell Transplantation · doi:10.1177/096368979900800115 · Cited by 24
Self-citationCorticosteroid Receptor Transgenic Mice
Urani, A., & Gass, P. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1286.037 · Cited by 21
Effect of immunosuppressive agents on glucocorticoid receptor function in A6 cells
Edinger, R. S., Watkins, S. C., Pearce, D., & Johnson, J. P. (2002) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00337.2001 · Cited by 8 · cited 4×
“On the other hand the evidence whether FK506 would enhance or inhibit nuclear translocation of the GR is still conflicting (Edinger et al., 2002).”
BackgroundInfluentialChanges induced in the central nervous system of rats by steroid drug
Miyakawa, T., Sumiyoshi, S., & Deshimaru, M. (1974) · Acta Neuropathologica · doi:10.1007/bf00685325 · Cited by 5
Research works printed but not linked: 1
- Limited, A.S., 2008. Antibody Review to Mouse Anti FKBP51 ab46002. Vol., ed.^eds. AbCam Incorporated, Cambridge, MA.
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Metadata
- Authors
- Tatro, E. T., Everall, I. P., Kaul, M., & Achim, C. L.
- Affiliations
- University of Pittsburgh (US)
- University of California San Diego (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Tatro, Erick T.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 1286
- Pages
- 1-12
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2724600
- OpenAlex
- W2000320359
- Semantic Scholar
- ae62fcaaab9cb7f8eb6e5a37d39b2b7868c8dc1d
- Cited by
- 125
- References
- 61
- Citations by year
- 2026: 2 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 14 · 2015: 8 · 2014: 9 · 2013: 4 · 2012: 5
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Center for AIDS Research, University of Washington
- University of California, San Diego
- National Institute of Mental Health (R01MH079881, P30MH62512, MH076681, R41MH079728, R25MH074508, R21MH076681, R25MH081482, P30MH062512)
- National Institute of Allergy and Infectious Diseases (AI-36214, P30AI036214)
- National Institute of Neurological Disorders and Stroke (R01NS050621)
- National Institute of Biomedical Imaging and Bioengineering (T32EB001026)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- glucocorticoid receptor, nuclear translocation, FKBP51, FKBP52, FKBP4, immunophilins, major depressive disorder, hypothalamic-pituitary-adrenal axis, cortisol, hypercortisolism, neuronal gene expression, stress response, siRNA knockdown
- MeSH terms
- Tacrolimus Binding Protein 5, Cells, Cultured, Depressive Disorder, Major, Major Depressive Disorder, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Neurons, Pituitary-Adrenal System, Receptors, Glucocorticoid, Gene Expression, Protein Transport, Tacrolimus Binding Proteins, RNA, Small Interfering
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