Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders

  • Jeon, Se Jin (Department of Life and Nanopharmaceutical Science, College of Pharmacy) ;
  • Ryu, Jong Hoon (Department of Life and Nanopharmaceutical Science, College of Pharmacy) ;
  • Bahn, Geon Ho (Department of Neuropsychiatry, School of Medicine, Kyung Hee University)
  • Received : 2016.02.21
  • Accepted : 2016.07.28
  • Published : 2017.05.01
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Abstract

Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.

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References

  1. Barateiro, A., Brites, D. and Fernandes, A. (2016) Oligodendrocyte development and myelination in neurodevelopment: molecular mechanisms in health and disease. Curr. Pharm. Des. 22, 656-679. https://doi.org/10.2174/1381612822666151204000636
  2. Barbarese, E., Koppel, D. E., Deutscher, M. P., Smith, C. L., Ainger, K., Morgan, F. and Carson, J. H. (1995) Protein translation components are colocalized in granules in oligodendrocytes. J. Cell Sci. 108, 2781-2790.
  3. Barrette, B., Nave, K. A. and Edgar, J. M. (2013) Molecular triggers of neuroinflammation in mouse models of demyelinating diseases. Biol. Chem. 394, 1571-1581.
  4. Bicker, S., Lackinger, M., Weiss, K. and Schratt, G. (2014) MicroRNA-132, -134, and -138: a microRNA troika rules in neuronal dendrites. Cell. Mol. Life Sci. 71, 3987-4005. https://doi.org/10.1007/s00018-014-1671-7
  5. Brown, S. S. and Stanfield, A. C. (2015) Fragile X premutation carriers: A systematic review of neuroimaging findings. J. Neurol. Sci. 352, 19-28. https://doi.org/10.1016/j.jns.2015.03.031
  6. Cai, J., Zhu, Q., Zheng, K., Li, H., Qi, Y., Cao, Q. and Qiu, M. (2010) Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes. Glia 58, 458-468.
  7. Campagnoni, A. T., Verdi, J. M., Verity, A. N., Amur-Umarjee, S. and Byravan, S (1991) Posttranscriptional regulation of myelin protein gene expression. Ann. N. Y. Acad. Sci. 633, 178-188. https://doi.org/10.1111/j.1749-6632.1991.tb15608.x
  8. Chen, E. and Joseph, S. (2015) Fragile X mental retardation protein: a paradigm for translational control by RNA-binding proteins. Biochimie 114, 147-154. https://doi.org/10.1016/j.biochi.2015.02.005
  9. Chen, L., Yun, S. W., Seto, J., Liu, W. and Toth, M. (2003) The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences. Neuroscience 120, 1005-1017. https://doi.org/10.1016/S0306-4522(03)00406-8
  10. Colman, D. R., Kreibich, G., Frey, A. B. and Sabatini, D. D. (1982) Synthesis and incorporation of myelin polypeptides into CNS myelin. J. Cell Biol. 95, 598-608. https://doi.org/10.1083/jcb.95.2.598
  11. Contractor, A., Klyachko, V. A. and Portera-Cailliau, C. (2015) Altered neuronal and circuit excitability in fragile X syndrome. Neuron 87, 699-715. https://doi.org/10.1016/j.neuron.2015.06.017
  12. Cullen, M. J. and Webster, H. D. (1989) Inhibition of protein synthesis during CNS myelination produces focal accumulations of membrane vesicles in oligodendrocytes. J. Neurocytol. 18, 763-774. https://doi.org/10.1007/BF01187229
  13. Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., Licatalosi, D. D., Richter, J. D. and Darnell, R. B. (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247-261. https://doi.org/10.1016/j.cell.2011.06.013
  14. Dugas, J. C., Cuellar, T. L., Scholze, A., Ason, B., Ibrahim, A., Emery, B., Zamanian, J. L., Foo, L. C., McManus, M. T. and Barres, B. A. (2010) Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron 65, 597-611. https://doi.org/10.1016/j.neuron.2010.01.027
  15. Fancy, S. P., Baranzini, S. E., Zhao, C., Yuk, D. I., Irvine, K. A., Kaing, S., Sanai, N., Franklin, R. J. and Rowitch, D. H. (2009) Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev. 23, 1571-1585. https://doi.org/10.1101/gad.1806309
  16. Edbauer, D., Neilson, J. R., Foster, K. A., Wang, C. F., Seeburg, D. P., Batterton, M. N., Tada, T., Dolan, B. M., Sharp, P. A. and Sheng, M. (2010) Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron 65, 373-384. https://doi.org/10.1016/j.neuron.2010.01.005
  17. Emery, B. (2010) Regulation of oligodendrocyte differentiation and myelination. Science 330, 779-782. https://doi.org/10.1126/science.1190927
  18. Ettle, B., Schlachetzki, J. C. and Winkler, J. (2016) Oligodendroglia and myelin in neurodegenerative diseases: more than just bystanders? Mol. Neurobiol. 53, 3046-3062. https://doi.org/10.1007/s12035-015-9205-3
  19. Fields, R. D. (2008) White matter in learning, cognition and psychiatric disorders. Trends Neurosci. 31, 361-370. https://doi.org/10.1016/j.tins.2008.04.001
  20. Friedrich, R. P., Schlierf, B., Tamm, E. R., Bosl, M. R. and Wegner, M. (2005) The class III POU domain protein Brn-1 can fully replace the related Oct-6 during schwann cell development and myelination. Mol. Cell. Biol. 25, 1821-1829. https://doi.org/10.1128/MCB.25.5.1821-1829.2005
  21. Geva, M., Cabilly, Y., Assaf, Y., Mindroul, N., Marom, L., Raini, G., Pinchasi, D. and Elroy-Stein, O. (2010) A mouse model for eukaryotic translation initiation factor 2B-leucodystrophy reveals abnormal development of brain white matter. Brain 133, 2448-2461. https://doi.org/10.1093/brain/awq180
  22. Giampetruzzi, A., Carson, J. H. and Barbarese, E. (2013) FMRP and myelin protein expression in oligodendrocytes. Mol. Cell. Neurosci. 56, 333-341. https://doi.org/10.1016/j.mcn.2013.07.009
  23. Gonzalez-Billault, C., Owen, R., Gordon-Weeks, P. R. and Avila, J. (2002) Microtubule-associated protein 1B is involved in the initial stages of axonogenesis in peripheral nervous system cultured neurons. Brain Res. 943, 56-67. https://doi.org/10.1016/S0006-8993(02)02534-9
  24. Hagerman, P. J. and Hagerman, R. J. (2015) Fragile X-associated tremor/ataxia syndrome. Ann. N. Y. Acad. Sci. 1338, 58-70. https://doi.org/10.1111/nyas.12693
  25. Hakak, Y., Walker, J. R., Li, C., Wong, W. H., Davis, K. L., Buxbaum, J. D., Haroutunian, V. and Fienberg, A. A. (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 98, 4746-4751. https://doi.org/10.1073/pnas.081071198
  26. Haroutunian, V., Katsel, P., Roussos, P., Davis, K. L., Altshuler, L. L. and Bartzokis, G. (2014) Myelination, oligodendrocytes, and serious mental illness. Glia 62, 1856-1877. https://doi.org/10.1002/glia.22716
  27. Huang, Y. S. and Richter, J. D. (2007) Analysis of mRNA translation in cultured hippocampal neurons. Meth. Enzymol. 431, 143-162.
  28. Jin, P., Zarnescu, D. C., Ceman, S., Nakamoto, M., Mowrey, J., Jongens, T. A., Nelson, D. L., Moses, K. and Warren, S. T. (2004) Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat. Neurosci. 7, 113-117. https://doi.org/10.1038/nn1174
  29. Kamm, C. and Zettl, U. K. (2012) Autoimmune disorders affecting both the central and peripheral nervous system. Autoimmun. Rev. 11, 196-202. https://doi.org/10.1016/j.autrev.2011.05.012
  30. Kleopa, K. A., Orthmann-Murphy, J. and Sargiannidou, I. (2010) Gap junction disorders of myelinating cells. Rev. Neurosci. 21, 397-419.
  31. Kocerha, J., Faghihi, M. A., Lopez-Toledano, M. A., Huang, J., Ramsey, A. J., Caron, M. G., Sales, N., Willoughby, D., Elmen, J., Hansen, H. F., Orum, H., Kauppinen, S., Kenny, P. J. and Wahlestedt, C. (2009) MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction. Proc. Natl. Acad. Sci. U.S.A. 106, 3507-3512. https://doi.org/10.1073/pnas.0805854106
  32. Kohlhauser, C., Mosgoller, W., Hoger, H. and Lubec, B. (2000) Myelination deficits in brain of rats following perinatal asphyxia. Life. Sci. 67, 2355-2368. https://doi.org/10.1016/S0024-3205(00)00816-X
  33. Kumar, S., Mattan, N. S. and de Vellis, J. (2006) Canavan disease: a white matter disorder. Ment. Retard. Dev. Disabil. Res. Rev. 12, 157-165. https://doi.org/10.1002/mrdd.20108
  34. Kunde, S. A., Musante, L., Grimme, A., Fischer, U., Muller, E., Wanker, E. E. and Kalscheuer, V. M. (2011) The X-chromosome-linked intellectual disability protein PQBP1 is a component of neuronal RNA granules and regulates the appearance of stress granules. Hum. Mol. Genet. 20, 4916-4931. https://doi.org/10.1093/hmg/ddr430
  35. Larocque, D., Pilotte, J., Chen, T., Cloutier, F., Massie, B., Pedraza, L., Couture, R., Lasko, P., Almazan, G. and Richard, S. (2002) Nuclear retention of MBP mRNAs in the quaking viable mice. Neuron 36, 815-829. https://doi.org/10.1016/S0896-6273(02)01055-3
  36. Larocque, D. and Richard, S. (2005) QUAKING KH domain proteins as regulators of glial cell fate and myelination. RNA Biol. 2, 37-40. https://doi.org/10.4161/rna.2.2.1603
  37. Lau, P., Verrier, J. D., Nielsen, J. A., Johnson, K. R., Notterpek, L. and Hudson, L. D. (2008) Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J. Neurosci. 28, 11720-11730. https://doi.org/10.1523/JNEUROSCI.1932-08.2008
  38. Laursen, L. S., Chan, C. W. and Ffrench-Constant, C. (2011) Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K. J. Cell Biol. 192, 797-811. https://doi.org/10.1083/jcb.201007014
  39. Li, Z., Zhang, Y., Ku, L., Wilkinson, K. D., Warren, S. T. and Feng, Y. (2001) The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic Acids Res. 29, 2276-2283. https://doi.org/10.1093/nar/29.11.2276
  40. Lozano, R., Rosero, C. A. and Hagerman, R. J. (2014) Fragile X spectrum disorders. Intractable Rare Dis. Res. 3, 134-146. https://doi.org/10.5582/irdr.2014.01022
  41. Lu, R., Wang, H., Liang, Z., Ku, L., O'Donnell, W. T., Li, W., Warren, S. T. and Feng, Y. (2004) The fragile X protein controls microtubuleassociated protein 1B translation and microtubule stability in brain neuron development. Proc. Natl. Acad. Sci. U.S.A. 101, 15201-15206. https://doi.org/10.1073/pnas.0404995101
  42. Luo, Y., Shan, G., Guo, W., Smrt, R. D., Johnson, E. B., Li, X., Pfeiffer, R. L., Szulwach, K. E., Duan, R., Barkho, B. Z., Li, W., Liu, C., Jin, P. and Zhao, X. (2010) Fragile X mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells. PLoS Genet. 6, e1000898. https://doi.org/10.1371/journal.pgen.1000898
  43. Mighdoll, M. I., Tao, R., Kleinman, J. E. and Hyde, T. M. (2015) Myelin, myelin-related disorders, and psychosis. Schizophr Res. 161, 85-93. https://doi.org/10.1016/j.schres.2014.09.040
  44. Miyashiro, K. Y., Beckel-Mitchener, A., Purk, T. P., Becker, K. G., Barret, T., Liu, L., Carbonetto, S., Weiler, I. J., Greenough, W. T. and Eberwine, J. (2003) RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37, 417-431. https://doi.org/10.1016/S0896-6273(03)00034-5
  45. Morris, J. K., Chomyk, A., Song, P., Parker, N., Deckard, S., Trapp, B. D., Pimplikar, S. W. and Dutta, R. (2015) Decrease in levels of the evolutionarily conserved microRNA miR-124 affects oligodendrocyte numbers in Zebrafish, Danio rerio. Invert Neurosci. 15, 4. https://doi.org/10.1007/s10158-015-0180-1
  46. Nave, K. A. and Werner, H. B. (2014) Myelination of the nervous system: mechanisms and functions. Annu. Rev. Cell Dev. Biol. 30, 503-533. https://doi.org/10.1146/annurev-cellbio-100913-013101
  47. Onnink, A. M., Zwiers, M. P., Hoogman, M., Mostert, J. C., Dammers, J., Kan, C. C., Vasquez, A. A., Schene, A. H., Buitelaar, J. and Franke, B. (2015) Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance. Prog. Neuropsychopharmacol. Biol. Psychiatry 63, 14-22. https://doi.org/10.1016/j.pnpbp.2015.04.008
  48. Pacey, L. K., Xuan, I. C., Guan, S., Sussman, D., Henkelman, R. M., Chen, Y., Thomsen, C. and Hampson, D. R. (2013) Delayed myelination in a mouse model of fragile X syndrome. Hum. Mol. Genet. 22, 3920-3930. https://doi.org/10.1093/hmg/ddt246
  49. Patel, A. B., Loerwald, K. W., Huber, K. M. and Gibson, J. R. (2014) Postsynaptic FMRP promotes the pruning of cell-to-cell connections among pyramidal neurons in the L5A neocortical network. J. Neurosci. 34, 3413-3418. https://doi.org/10.1523/JNEUROSCI.2921-13.2014
  50. Pombo, P. M, Barettino, D., Ibarrola, N., Vega, S. and Rodríguez-Pena, A. (1999) Stimulation of the myelin basic protein gene expression by 9-cis-retinoic acid and thyroid hormone: activation in the context of its native promoter. Brain Res. Mol. Brain Res. 64, 92-100. https://doi.org/10.1016/S0169-328X(98)00311-8
  51. Qi, Y., Cai, J., Wu, Y., Wu, R., Lee, J., Fu, H., Rao, M., Sussel, L., Rubenstein, J. and Qiu, M. (2001) Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 128, 2723-2733.
  52. Ren, Y., Wang, H. and Xiao, L. (2013) Improving myelin/oligodendrocyte-related dysfunction: a new mechanism of antipsychotics in the treatment of schizophrenia? Int. J. Neuropsychopharmacol. 16, 691-700. https://doi.org/10.1017/S1461145712001095
  53. Richter, J. D., Bassell, G. J. and Klann, E. (2015) Dysregulation and restoration of translational homeostasis in fragile X syndrome. Nat. Rev. Neurosci. 16, 595-605. https://doi.org/10.1038/nrn4001
  54. Rowley, C. D., Bazin, P. L., Tardif, C. L., Sehmbi, M., Hashim, E., Zaharieva, N., Minuzzi, L., Frey, B. N. and Bock, N. A. (2015) Assessing intracortical myelin in the living human brain using myelinated cortical thickness. Front. Neurosci. 9, 396.
  55. Saldarriaga, W., Tassone, F., Gonzalez-Teshima, L. Y., Forero-Forero, J. V., Ayala-Zapata, S. and Hagerman, R. (2014) Fragile X syndrome. Colomb. Med. 45, 190-198.
  56. Scharf, S. H., Jaeschke, G., Wettstein, J. G. and Lindemann, L. (2015) Metabotropic glutamate receptor 5 as drug target for Fragile X syndrome. Curr. Opin. Pharmacol. 20, 124-134. https://doi.org/10.1016/j.coph.2014.11.004
  57. Soontarapornchai, K., Maselli, R., Fenton-Farrell, G., Tassone, F., Hagerman, P. J., Hessl, D. and Hagerman, R. J. (2008) Abnormal nerve conduction features in fragile X premutation carriers. Arch. Neurol. 65, 495-498. https://doi.org/10.1001/archneur.65.4.495
  58. Stolt, C. C., Schlierf, A., Lommes, P., Hillgärtner, S., Werner, T., Kosian, T., Sock, E., Kessaris, N., Richardson, W. D., Lefebvre, V. and Wegner, M. (2006) SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Dev. Cell. 11, 697-709. https://doi.org/10.1016/j.devcel.2006.08.011
  59. Stolt, C. C. and Wegner, M. (2010) SoxE function in vertebrate nervous system development. Int. J. Biochem. Cell Biol. 42, 437-440. https://doi.org/10.1016/j.biocel.2009.07.014
  60. Svaren, J. (2014) MicroRNA and transcriptional crosstalk in myelinating glia. Neurochem. Int. 77, 50-57. https://doi.org/10.1016/j.neuint.2014.06.010
  61. Tawk, M., Makoukji, J., Belle, M., Fonte, C., Trousson, A., Hawkins, T., Li, H., Ghandour, S., Schumacher, M. and Massaad, C. (2011) Wnt/beta-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis. J. Neurosci. 31, 3729-3742. https://doi.org/10.1523/JNEUROSCI.4270-10.2011
  62. Telias, M., Mayshar, Y., Amit, A. and Ben-Yosef, D. (2015) Molecular mechanisms regulating impaired neurogenesis of fragile X syndrome human embryonic stem cells. Stem Cells Dev. 24, 2353-2365. https://doi.org/10.1089/scd.2015.0220
  63. Toritsuka, M., Makinodan, M. and Kishimoto, T. (2015) Social experience-dependent myelination: an implication for psychiatric disorders. Neural Plast. 2015, 465345.
  64. Tranfaglia, M. R. (2011) The psychiatric presentation of fragile X: evolution of the diagnosis and treatment of the psychiatric comorbidities of fragile X syndrome. Dev. Neurosci. 33, 337-348. https://doi.org/10.1159/000329421
  65. Tranfaglia, M. R. (2012) Fragile X syndrome: a psychiatric perspective. Results Probl. Cell Differ. 54, 281-295.
  66. Voineskos, A. N. (2015) Genetic underpinnings of white matter 'connectivity': heritability, risk, and heterogeneity in schizophrenia. Schizophr. Res. 161, 50-60. https://doi.org/10.1016/j.schres.2014.03.034
  67. Wang, H., Ku, L., Osterhout, D. J., Li, W., Ahmadian, A., Liang, Z. and Feng, Y. (2004) Developmentally-programmed FMRP expression in oligodendrocytes: a potential role of FMRP in regulating translation in oligodendroglia progenitors. Hum. Mol. Genet. 13, 79-89.
  68. Wei, Q., Miskimins, W. K. and Miskimins, R. (2005) Stage-specific expression of myelin basic protein in oligodendrocytes involves Nkx2.2-mediated repression that is relieved by the Sp1 transcription factor. J. Biol. Chem. 280, 16284-16294. https://doi.org/10.1074/jbc.M500491200
  69. Wu, H. Y., Dawson, M. R., Reynolds, R. and Hardy, R. J. (2001) Expression of QKI proteins and MAP1B identifies actively myelinating oligodendrocytes in adult rat brain. Mol. Cell. Neurosci. 17, 292-302. https://doi.org/10.1006/mcne.2000.0941
  70. Yi, Y. H., Sun, X. S., Qin, J. M., Zhao, Q. H., Liao, W. P. and Long, Y. S. (2010) Experimental identification of microRNA targets on the 3' untranslated region of human FMR1 gene. J. Neurosci. Methods 190, 34-38. https://doi.org/10.1016/j.jneumeth.2010.04.022
  71. Zearfoss, N. R., Farley, B. M. and Ryder, S. P. (2008) Post-transcriptional regulation of myelin formation. Biochim. Biophys. Acta 1779, 486-494. https://doi.org/10.1016/j.bbagrm.2008.06.003
  72. Zhao, X., He, X., Han, X., Yu, Y., Ye, F., Chen, Y., Hoang, T., Xu, X., Mi, Q. S., Xin, M., Wang, F., Appel, B. and Lu, Q. R. (2010) MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65, 612-626. https://doi.org/10.1016/j.neuron.2010.02.018
  73. Zhou, R., Yuan, P., Wang, Y., Hunsberger, J. G., Elkahloun, A., Wei, Y., Damschroder-Williams, P., Du, J., Chen, G. and Manji, H. K. (2009) Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacology 34, 1395-1405. https://doi.org/10.1038/npp.2008.131

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