Journal of Molecular Neuroscience

, Volume 35, Issue 1, pp 55–63

The Cytoskeleton in Oligodendrocytes

Microtubule Dynamics in Health and Disease
Article

Abstract

Oligodendrocytes have a complex cytoarchitecture and are characterized by an elaborate network of microtubules. They provide the tracks for organelle trafficking and the intracellular translocation of myelin-specific gene products. The integrity of the cytoskeleton is an essential determinant of the function and survival of oligodendrocytes. Microtubule growth and stability are regulated by microtubule-associated proteins. Oligodendrocytes contain a number of microtubule-associated proteins, including the tau proteins, which are developmentally regulated and especially prominent in the branching points of the cellular processes. Process outgrowth is regulated by the interaction of Fyn kinase with the cytoskeleton and by microtubule-severing proteins, such as stathmin. Alterations or disruption of the cytoskeleton and abundant abnormal aggregates of cytoskeletal proteins often accompany neurodegenerative diseases, and inclusion bodies, resembling protein aggregates found in neurons, are prominent in oligodendroglial lesions in white matter pathology. This review emphasizes the role of the cytoskeleton, particularly of microtubules and their associated proteins, in oligodendrocytes during developmental processes. Furthermore, recent data on protein aggregate formation in oligodendroglial cells, which might occur during aging and disease processes, are summarized.

Keywords

Myelin Tubulin Microtubule associated proteins Tau Heat shock proteins Glial inclusion body 

References

  1. Albers, D. S., & Augood, S. J. (2001). New insights into progressive supranuclear palsy. Trends in Neurosciences, 24, 347–353.PubMedCrossRefGoogle Scholar
  2. Andersen, S. S. (2000). Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends in Cell Biology, 10, 261–267.PubMedCrossRefGoogle Scholar
  3. Baas, P. W. (1999). Microtubules and neuronal polarity: lessons from mitosis. Neuron, 22, 23–31.PubMedCrossRefGoogle Scholar
  4. Barry, C., Pearson, C., & Barbarese, E. (1996). Morphological organization of oligodendrocyte processes during development in culture and in vivo. Developmental Neuroscience, 18, 233–242.PubMedCrossRefGoogle Scholar
  5. Bauer, N. G., & Richter-Landsberg, C. (2006). The dynamic instability of microtubules is required for aggresome formation in oligodendroglial cells after proteolytic stress. Journal of Molecular Neuroscience, 29, 153–168.PubMedCrossRefGoogle Scholar
  6. Buée, L., Bussiere, T., Buee-Scherrer, V., Delacourte, A., & Hof, P. R. (2000). Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain research. Brain research reviews, 33, 95–130.PubMedCrossRefGoogle Scholar
  7. Cairns, N. J., Atkinson, P. F., Hanger, D. P., Anderton, B. H., Daniel, S. E., & Lantos, P. L. (1997). Tau protein in the glial cytoplasmic inclusions of multiple system atrophy can be distinguished from abnormal tau in Alzheimer’s disease. Neuroscience Letters, 230, 49–52.PubMedCrossRefGoogle Scholar
  8. Carson, J. H., Worboys, K., Ainger, K., & Barbarese, E. (1997). Translocation of myelin basic protein mRNA in oligodendrocytes requires microtubules and kinesin. Cell Motility and the Cytoskeleton, 38, 318–328.PubMedCrossRefGoogle Scholar
  9. Chin, S. S., & Goldman, J. E. (1996). Glial inclusions in CNS degenerative diseases. Journal of Neuropathology and Experimental Neurology, 55, 499–508.PubMedGoogle Scholar
  10. Ciechanover, A., & Brundin, P. (2003). The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron, 40, 427–446.PubMedCrossRefGoogle Scholar
  11. Dabir, D. V., Trojanowski, J. Q., Richter-Landsberg, C., Lee, V. M., & Forman, M. S. (2004). Expression of the small heat-shock protein alphaB-crystallin in tauopathies with glial pathology. American Journal of Pathology, 164, 155–166.PubMedGoogle Scholar
  12. Dickson, D. W., Lin, W., Liu, W. K., & Yen, S. H. (1999). Multiple system atrophy: a sporadic synucleinopathy. Brain Pathology, 9, 721–732.PubMedCrossRefGoogle Scholar
  13. Dyer, C. A., & Benjamins, J. A. (1989). Organization of oligodendroglial membrane sheets. I: Association of myelin basic protein and 2′,3′-cyclic nucleotide 3′-phosphohydrolase with cytoskeleton. Journal of Neuroscience Research, 24, 201–211.PubMedCrossRefGoogle Scholar
  14. Fass, E., Shvets, E., Degani, I., Hirschberg, K., & Elazar, Z. (2006). Microtubules support production of starvation-induced autophagosomes but not their targeting and fusion with lysosomes. Journal of Biological Chemistry, 281, 36303–36316.PubMedCrossRefGoogle Scholar
  15. Fischer, I., Konola, J., & Cochary, E. (1990). Microtubule associated protein (MAP1B) is present in cultured oligodendrocytes and co-localizes with tubulin. Journal of Neuroscience Research, 27, 112–124.PubMedCrossRefGoogle Scholar
  16. Forman, M. S., Trojanowski, J. Q., & Lee, V. M. (2004). Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Natural Medicines, 10, 1055–1063.CrossRefGoogle Scholar
  17. Galiano, M. R., Andrieux, A., Deloulme, J. C., Bosc, C., Schweitzer, A., Job, D. et al. (2006). Myelin basic protein functions as a microtubule stabilizing protein in differentiated oligodendrocytes. Journal of Neuroscience Research, 84, 534–541.PubMedCrossRefGoogle Scholar
  18. Garcia-Mata, R., Bebok, Z., Sorscher, E. J., & Sztul, E. S. (1999). Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. Journal of Cell Biology, 146, 1239–1254.PubMedCrossRefGoogle Scholar
  19. Giasson, B. I., Lee, V. M. Y., & Trojanowski, J. Q. (2004). Animal models of neurodegenerative dementing disorders othe than Alzheimer`s disease. Clinical Neuroscience Research, 3, 427–436.CrossRefGoogle Scholar
  20. Goedert, M. (2001). The significance of tau and alpha-synuclein inclusions in neurodegenerative diseases. Current Opinion in Genetics & Development, 11, 343–351.CrossRefGoogle Scholar
  21. Goedert, M., Crowther, R. A., & Garner, C. C. (1991). Molecular characterization of microtubule-associated proteins tau and MAP2. Trends in Neurosciences, 14, 193–199.PubMedCrossRefGoogle Scholar
  22. Goedert, M., Spillantini, M. G., & Davies, S. W. (1998). Filamentous nerve cell inclusions in neurodegenerative diseases. Current Opinion in Neurobiology, 8, 619–632.PubMedCrossRefGoogle Scholar
  23. Goldbaum, O., Oppermann, M., Handschuh, M., Dabir, D., Zhang, B., Forman, M. S. et al. (2003). Proteasome inhibition stabilizes tau inclusions in oligodendroglial cells that occur after treatment with okadaic acid. Journal of Neuroscience, 23, 8872–8880.PubMedGoogle Scholar
  24. Goldbaum, O., & Richter-Landsberg, C. (2004). Proteolytic stress causes heat shock protein induction, tau ubiquitination, and the recruitment of ubiquitin to tau-positive aggregates in oligodendrocytes in culture. Journal of Neuroscience, 24, 5748–5757.PubMedCrossRefGoogle Scholar
  25. Gorath, M., Stahnke, T., Mronga, T., Goldbaum, O., & Richter-Landsberg, C. (2001). Developmental changes of tau protein and mRNA in cultured rat brain oligodendrocytes. Glia, 36, 89–101.PubMedCrossRefGoogle Scholar
  26. Götz, J., Tolnay, M., Barmettler, R., Chen, F., Probst, A., & Nitsch, R. M. (2001). Oligodendroglial tau filament formation in transgenic mice expressing G272V tau. European Journal of Neuroscience, 13, 2131–2140.PubMedCrossRefGoogle Scholar
  27. Grinspan, J. (2002). Cells and signaling in oligodendrocyte development. Journal of Neuropathology and Experimental Neurology, 61, 297–306.PubMedGoogle Scholar
  28. Higuchi, M., Ishihara, T., Zhang, B., Hong, M., Andreadis, A., Trojanowski, J. et al. (2002). Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration. Neuron, 35, 433–446.PubMedCrossRefGoogle Scholar
  29. Higuchi, M., Zhang, B., Forman, M. S., Yoshiyama, Y., Trojanowski, J. Q., & Lee, V. M. (2005). Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies. Journal of Neuroscience, 25, 9434–9443.PubMedCrossRefGoogle Scholar
  30. Hirokawa, N., Noda, Y., & Okada, Y. (1998). Kinesin and dynein superfamily proteins in organelle transport and cell division. Current Opinion in Cell Biology, 10, 60–73.PubMedCrossRefGoogle Scholar
  31. Irving, E. A., Nicoll, J., Graham, D. I., & Dewar, D. (1996). Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury. Neuroscience Letters, 213, 189–192.PubMedGoogle Scholar
  32. Johnston, J. A., Ward, C. L., & Kopito, R. R. (1998). Aggresomes: a cellular response to misfolded proteins. Journal of Cell Biology, 143, 1883–1898.PubMedCrossRefGoogle Scholar
  33. Keller, J. N., Gee, J., & Ding, Q. (2002). The proteasome in brain aging. Ageing Research Reviews, 1, 279–293.PubMedCrossRefGoogle Scholar
  34. Klein, C., Kramer, E. M., Cardine, A. M., Schraven, B., Brandt, R., & Trotter, J. (2002). Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau. Journal of Neuroscience, 22, 698–707.PubMedGoogle Scholar
  35. Komori, T. (1999). Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick’s disease. Brain Pathology, 9, 663–679.PubMedCrossRefGoogle Scholar
  36. Kopito, R. R. (2000). Aggresomes, inclusion bodies and protein aggregation. Trends in Cell Biology, 10, 524–530.PubMedCrossRefGoogle Scholar
  37. Kramer, E. M., Klein, C., Koch, T., Boytinck, M., & Trotter, J. (1999). Compartmentation of Fyn kinase with glycosylphosphatidylinositol-anchored molecules in oligodendrocytes facilitates kinase activation during myelination. Journal of Biological Chemistry, 274, 29042–29049.PubMedCrossRefGoogle Scholar
  38. Laferriere, N. B., MacRae, T. H., & Brown, D. L. (1997). Tubulin synthesis and assembly in differentiating neurons. Biochemistry and Cell Biology, 75, 103–117.PubMedCrossRefGoogle Scholar
  39. Lantos, P. L. (1998). The definition of multiple system atrophy: a review of recent developments. Journal of Neuropathology and Experimental Neurology, 57, 1099–1111.PubMedGoogle Scholar
  40. Lee, V. M., Giasson, B. I., & Trojanowski, J. Q. (2004). More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases. Trends Neuroscience, 27, 129–134.CrossRefGoogle Scholar
  41. Lee, V. M., Goedert, M., & Trojanowski, J. Q. (2001). Neurodegenerative tauopathies. Annual Review of Neuroscience, 24, 1121–1159.PubMedCrossRefGoogle Scholar
  42. Lee, J., Gravel, M., Zhang, R., Thibault, P., & Braun, P. E. (2005). Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein. Journal of Cell Biology, 170, 661–673.PubMedCrossRefGoogle Scholar
  43. Lee, J. C., Mayer-Proschel, M., & Rao, M. S. (2000). Gliogenesis in the central nervous system. Glia, 30, 105–121.PubMedCrossRefGoogle Scholar
  44. Liang, X., Draghi, N. A., & Resh, M. D. (2004). Signaling from integrins to Fyn to Rho family GTPases regulates morphologic differentiation of oligodendrocytes. Journal of Neuroscience, 24, 7140–7149.PubMedCrossRefGoogle Scholar
  45. Lin, W. L., Lewis, J., Yen, S. H., Hutton, M., & Dickson, D. W. (2003). Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutation. American Journal of Pathology, 162, 213–218.PubMedGoogle Scholar
  46. Liu, A., Muggironi, M., Marin-Husstege, M., & Casaccia-Bonnefil, P. (2003). Oligodendrocyte process outgrowth in vitro is modulated by epigenetic regulation of cytoskeletal severing proteins. Glia, 44, 264–274.PubMedCrossRefGoogle Scholar
  47. Liu, A., Stadelmann, C., Moscarello, M., Bruck, W., Sobel, A., Mastronardi, F. G. et al. (2005). Expression of stathmin, a developmentally controlled cytoskeleton-regulating molecule, in demyelinating disorders. Journal of Neuroscience, 25, 737–747.PubMedCrossRefGoogle Scholar
  48. LoPresti, P., Szuchet, S., Papasozomenos, S. C., Zinkowski, R. P., & Binder, L. I. (1995). Functional implications for the microtubule-associated protein tau: localization in oligodendrocytes. Proceedings of the National Academy of Sciences of the United States of America, 92, 10369–10373.PubMedCrossRefGoogle Scholar
  49. Lüders, J., & Stearns, T. (2007). Microtubule-organizing centres: a re-evaluation. Nature reviews. Molecular cell biology, 8, 161–167.PubMedCrossRefGoogle Scholar
  50. Lunn, K. F., Baas, P. W., & Duncan, I. D. (1997). Microtubule organization and stability in the oligodendrocyte. Journal of Neuroscience, 17, 4921–4932.PubMedGoogle Scholar
  51. Miller, D. W., Cookson, M. R., & Dickson, D. W. (2004). Glial cell inclusions and the pathogenesis of neurodegenerative diseases. Neuron Glia Biology, 1, 13–21.PubMedCrossRefGoogle Scholar
  52. Muller, R., Heinrich, M., Heck, S., Blohm, D., & Richter-Landsberg, C. (1997). Expression of microtubule-associated proteins MAP2 and tau in cultured rat brain oligodendrocytes. Cell & Tissue Research, 288, 239–249.CrossRefGoogle Scholar
  53. Nixon, R. A. (2006). Autophagy in neurodegenerative disease: friend, foe or turncoat? Trends in Neurosciences, 29, 528–535.PubMedCrossRefGoogle Scholar
  54. Osterhout, D. J., Wolven, A., Wolf, R. M., Resh, M. D., & Chao, M. V. (1999). Morphological differentiation of oligodendrocytes requires activation of Fyn tyrosine kinase. Journal of Cell Biology, 145, 1209–1218.PubMedCrossRefGoogle Scholar
  55. Ozon, S., Guichet, A., Gavet, O., Roth, S., & Sobel, A. (2002). Drosophila stathmin: a microtubule-destabilizing factor involved in nervous system formation. Molecular Biology of the Cell, 13, 698–710.PubMedCrossRefGoogle Scholar
  56. Pfeiffer, S. E., Warrington, A. E., & Bansal, R. (1993). The oligodendrocyte and its many cellular processes. Trends in Cell Biology, 3, 191–197.PubMedCrossRefGoogle Scholar
  57. Quarles R. H., Macklin W. B., & Morell P. (2006). Myelin formation, structure and biochemistry. In G. J. Siegel, R. W. Albers, S. T. Brady, & D. L. Price (Eds.), Basic Neurochemistry (7th ed., pp. 51–71). New York: Elsevier.Google Scholar
  58. Raynaud-Messina, Merdes, A. (2007). γ-Tubulin complexes and microtubule organization. Current Opinion in Cell Biology, 19, 24–30.PubMedCrossRefGoogle Scholar
  59. Richter-Landsberg C. (2000). The oligodendroglia cytoskeleton in health and disease. Journal of Neuroscience Research, 59, 11–18.PubMedCrossRefGoogle Scholar
  60. Richter-Landsberg C. (2007). Heat shock proteins: expression and functional roles in nerve cells and glia. In C. Richter-Landsberg (Ed.), Heat Shock Proteins in Neural Cells (pp 1–12). New York: Springer.Google Scholar
  61. Richter-Landsberg, C., & Bauer, N. G. (2004). Tau-inclusion body formation in oligodendroglia: the role of stress proteins and proteasome inhibition. International Journal of Developmental Neuroscience, 22, 443–451.PubMedCrossRefGoogle Scholar
  62. Richter-Landsberg, C., & Goldbaum, O. (2003). Stress proteins in neural cells: functional roles in health and disease. Cellular and Molecular Life Sciences, 60, 337–349.PubMedCrossRefGoogle Scholar
  63. Richter-Landsberg, C., & Goldbaum, O. (2007). Small heat shock proteins and the cytoskeleton. In C. Richter-Landsberg (Ed.), Heat Shock Proteins in Neural Cells (pp. 13–24). New York: Springer.Google Scholar
  64. Richter-Landsberg, C., & Gorath, M. (1999). Developmental regulation of alternatively spliced isoforms of mRNA encoding MAP2 and tau in rat brain oligodendrocytes during culture maturation. Journal of Neuroscience Research, 56, 259–270.PubMedCrossRefGoogle Scholar
  65. Richter-Landsberg, C., & Heinrich, M. (1996). OLN-93: a new permanent oligodendroglia cell line derived from primary rat brain glial cultures. Journal of Neuroscience Research, 45, 161–173.PubMedCrossRefGoogle Scholar
  66. Ross, C. A., & Poirier, M. A. (2005). Opinion: What is the role of protein aggregation in neurodegeneration? Nature Reviews. Molecular Cell Biology, 6, 891–898.PubMedCrossRefGoogle Scholar
  67. Sherman, M. Y., & Goldberg, A. L. (2001). Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron, 29, 15–32.PubMedCrossRefGoogle Scholar
  68. Smith, R. (2004). Moving molecules: mRNA trafficking in Mammalian oligodendrocytes and neurons. Neuroscientist, 10, 495–500.PubMedCrossRefGoogle Scholar
  69. Song, J., Goetz, B. D., Baas, P. W., & Duncan, I. D. (2001). Cytoskeletal reorganization during the formation of oligodendrocyte processes and branches. Molecular and Cellular Neurosciences, 17, 624–636.PubMedCrossRefGoogle Scholar
  70. Song, J., O’Connor L. T., Yu, W., Baas, P. W., & Duncan, I. D. (1999). Microtubule alterations in cultured taiep rat oligodendrocytes lead to deficits in myelin membrane formation. Journal of Neurocytology, 28, 671–683.PubMedCrossRefGoogle Scholar
  71. Sperber, B. R., Boyle-Walsh, E. A., Engleka, M. J., Gadue, P., Peterson, A. C., Stein, P. L. et al. (2001). A unique role for Fyn in CNS myelination. Journal of Neuroscience, 21, 2039–2047.PubMedGoogle Scholar
  72. Sperber, B. R., & McMorris, F. A. (2001). Fyn tyrosine kinase regulates oligodendroglial cell development but is not required for morphological differentiation of oligodendrocytes. Journal of Neuroscience Research, 63, 303–312.PubMedCrossRefGoogle Scholar
  73. Takeda, A., Arai, N., Komori, T., Iseki, E., Kato, S., & Oda, M. (1997). Tau immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neuroscience Letters, 234, 63–66.PubMedCrossRefGoogle Scholar
  74. Terada, N., Kidd, G. J., Kinter, M., Bjartmar, C., Moran-Jones, K., & Trapp, B. D. (2005). Beta IV tubulin is selectively expressed by oligodendrocytes in the central nervous system. Glia, 50, 212–222.PubMedCrossRefGoogle Scholar
  75. Umemori, H., Sato, S., Yagi, T., Aizawa, S., & Yamamoto, T. (1994). Initial events of myelination involve Fyn tyrosine kinase signalling. Nature, 367, 572–576.PubMedCrossRefGoogle Scholar
  76. Vouyiouklis, D. A., & Brophy, P. J. (1993). Microtubule-associated protein MAP1B expression precedes the morphological differentiation of oligodendrocytes. Journal of Neuroscience Research, 35, 257–267.PubMedCrossRefGoogle Scholar
  77. Vouyiouklis, D. A., & Brophy, P. J. (1995). Microtubule-associated proteins in developing oligodendrocytes: transient expression of a MAP2c isoform in oligodendrocyte precursors. Journal of Neuroscience Research, 42, 803–817.PubMedCrossRefGoogle Scholar
  78. Wiese, C., & Zheng, Y. (2006). Microtubule nucleation: γ-tubulin and beyond. Journal of Cell Science, 119, 4143–4153.PubMedCrossRefGoogle Scholar
  79. Wilson, R., & Brophy, P. J. (1989). Role for the oligodendrocyte cytoskeleton in myelination. Journal of Neuroscience Research, 22, 439–448.PubMedCrossRefGoogle Scholar
  80. Zamora-Leon, S. P., Lee, G., Davies, P., & Shafit-Zagardo, B. (2001). Binding of Fyn to MAP-2c through an SH3 binding domain. Regulation of the interaction by ERK2. Journal of Biological Chemistry, 276, 39950–39958.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Department of Biology, Molecular NeurobiologyUniversity of OldenburgOldenburgGermany

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