Structural Organisation and Stability of Central Nervous System Myelin

  • M. G. Rumsby
Part of the NATO ASI Series book series (NSSA, volume 142)


Studies aimed at elucidating the structural organisation of the myelin sheath in the central and peripheral nervous systems have been steadily progressing for many years and were initiated using physicochemical techniques, primarly X-ray diffraction and electron microscopy (Finean, 1961). Because of its multilamellar structure the myelin sheath is highly amenable to analysis by X-ray techniques and many of the earlier studies were undertaken on myelin to glean information about the structure of biological membranes in general. We know now that myelin, with its very high lipid to protein ratio (Table 1), is at one end of a wide spectrum of biological membranes all of which appear to have a common structural organisation of complex lipids in a stable bilayer form in fluid-mosaic arrangement with proteins (Singer & Nicholson, 1972).


Myelin Basic Protein Acyl Chain Myelin Sheath Radial Component Bovine Brain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Banik, N. L., Gohil, K., and Davison, A. N., 1976, The action of snake venom, phospholipase A and trypsin on purified myelin in vitro, Biochem. J., 159: 273.Google Scholar
  2. Banik, N. L., McAlhaney, W. W., and Hogan, E. L. 1985, Calcium-stimulated proteolysis in myelin: evidence for a Ca2+ — activated neutral proteinase associated with purified myelin of rat CNS, J. Neurochem., 45: 581.CrossRefGoogle Scholar
  3. Beneveniste, E. N., Merril, J. E., Kaufman, S. E., Golde, D. W., and Gasson, J. C., 1985, Purification and characterization of a human T-lymphocyte-derived glial growth-promoting factor, Proc. Natl. Sci., 82: 3930.CrossRefGoogle Scholar
  4. Beneveniste, E. N. and Merrill, J. E., 1986, Interleukin-2 stimulation of oligodendroglial proliferation and maturation, Nature, 321: 610.CrossRefGoogle Scholar
  5. Bhat, S. and Pfeiffer, S. E., 1986, Stimulation of oligodendrocytes by extracts from astrocyte-enriched cultures, J. Neurosci. Res., 15: 19.CrossRefGoogle Scholar
  6. Blakemore, W. F., 1972, Observations on oligodendrocyte degeneration, the resolution of status spongiosus and remyelination in cuprizone intoxication in mice, J. Neurocytol., 1: 413.CrossRefGoogle Scholar
  7. Blank, W. F. Jr., Bunge, M. B., and Bunge, R. P., 1974, The sensitivity of the myelin sheath, particularly the Schwann cell axolemmal junction, to lowered calcium levels in cultured sensory ganglia, Brain Res., 67: 503.CrossRefGoogle Scholar
  8. Blaurock, A. E., 1979, On phasing the small-angle X-ray diffraction pattern from nerve myelin, Biophys. J., 26: 147.CrossRefGoogle Scholar
  9. Blauroch, A. E., 1981, The spaces between membrane bilayers within PNS myelin as characterized by X-ray diffraction, Brain Res., 210: 383.CrossRefGoogle Scholar
  10. Boggs, J. M., Stamp, D., Hughes, D. W., and Deber, C. M., 1981, Influence of ether linkage on the lamellar to hexagonal phase transition of ethanolamine phospholipids, Biochem., 20: 5728.CrossRefGoogle Scholar
  11. Boggs, J. M., Moscarello, M. A., Papahadjopoulos, D., 1982, Structural organization of myelin — role of lipid-protein interactions determined in model systems, in: “Lipid-Protein Interactions”, P. Jost and O. H. Griffith, eds., Academic Press, New York.Google Scholar
  12. Braun, P. E., 1984, Molecular organisation of myelin, in: “Myelin”, P. Morell, ed., Plenum Press, New York.Google Scholar
  13. Cammer, W., Brosnan, C. F., Basile, C., Bloom, B. R., and Norton, W. T., 1986, Complement potentiates the degradation of myelin proteins by plasmin: implications for a mechanism of inflammatory demyelination, Brain Res., 364: 91.CrossRefGoogle Scholar
  14. Cashman, N. R., and Noronha, A., 1986, Accessory cell competence of ovine oligodendrocytes in mitogenic activation of human peripheral T cells, J. Immunol., 136: 4460.Google Scholar
  15. Curatolo, W., 1986, The interactions of l-palmitoyl-2-oleoylphosphatidyl-choline and bovine brain cerebroside, Biochim. Biophys. Acta, 861: 373.CrossRefGoogle Scholar
  16. Cyong, J.C., Witkin, S. S., Rieger, B., Barbarese, E., Good, R. A., and Day, N. K., 1982, Antibody-independent complement activation by myelin via the classical complement pathway, J. Exp. Med., 155: 587.CrossRefGoogle Scholar
  17. Demel, R. A., and de Kruyff, B., 1976, The function of sterols in membranes, Biochim. Biophys. Acta, 457: 109.CrossRefGoogle Scholar
  18. Dermietzel, R., 1974, Junctions in the central nervous system of the cat, Cell Tissue Res., 148: 565.CrossRefGoogle Scholar
  19. Desjardins, K. C., and Morell, P., 1983, Phosphate groups modifyng myelin basic proteins are metabolically labile; methyl groups are stable, J.Cell Biol., 97: 438.CrossRefGoogle Scholar
  20. Epstein, L. G., Prineas, J. W., and Raine, C. S., 1983, Attachment of myelin to coated pits on macrophages in experimental allergic encephalomyelitis, J. Neurol. Sci., 61: 341.CrossRefGoogle Scholar
  21. Finean, J. B., 1961, The nature and stability of nerve myelin, Int. Rev. Cytol, 12,303.Google Scholar
  22. ffrench-Constant, C., and Raff, M. C., 1986, The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination, Nature, 323: 335.CrossRefGoogle Scholar
  23. Fontana, A., Fierz, W., and Wekerle, H., 1984, Astrocytes present myelin basic protein to encephalitogenic T-cell lines, Nature, 307: 273.CrossRefGoogle Scholar
  24. Golds, E. E., and Braun, P. E., 1978, Protein associations and basic protein conformation in the myelin membrane, the use ofdifluoro-dinitrobenzene as a cross-linking reagent, J. Biol. Chem., 253: 8162.Google Scholar
  25. Gregson, N. A., 1977, The surface properties of isolated rat brain myelin: a microelectrophoretic study, J. Neurochem., 29: 895.CrossRefGoogle Scholar
  26. Gregson, N. A., 1983, The Molecular Biology of Myelin, in: “Multiple Sclerosis. Pathology, diagnosis and management”, J. F. Hallpike, C. W. M. Adams & W. W. Tourtellotte, eds., Chapman & Hall, London.Google Scholar
  27. Grundke-Iqbal, I., Raine, C. S., Johnson, A. B., Brosnan, C. F., and Bornstein, M. B., 1981, Experimental allergic encephalomyelitis-Characterisation of serum factors causing demyelination and swelling of myelin, J. Neurol. Sci., 50: 63.CrossRefGoogle Scholar
  28. Gwarsha, K., Rumsby, M. G., and Little, C., 1984a, Action of phospholipase C (Bacillus Cereus) on isolated myelin sheath preparations, Neurochem. Int., 6: 199.CrossRefGoogle Scholar
  29. Gwarsha, K., Rumsby, M. G., and Little, C., 1984b, On the disposition of phospholipids in freshly isolated myelin sheath preparations from bovine brain, Neurochem. Int., 6: 599.CrossRefGoogle Scholar
  30. Hall, S. M. and Gregson, N. A., 1971, The in vivo and ultrastructural effects of injection of lysophosphatidylcholine into myelinated peripheral nerve fibres of the adult mouse, J. Cell Sci., 9: 769.Google Scholar
  31. Hall, S. M., 1972, The effect of injections of lysophosphatidylcholine into white matter of the adult mouse spinal cord, J. Cell Sci., 10: 535.Google Scholar
  32. Hauser, H., Pascher, I., Pearson, R. H., and Sundell, S., 1981, Preferred conformation and molecular packing of phosphatidylethanolamine and phosphatidylcholine, Biochim. Biophys. Acta, 650: 21.CrossRefGoogle Scholar
  33. Henn, F. A. and Thompson, T. E., 1969, Synthetic lipid bilayer membranes, Ann. Revs. Biochem., 38: 241.CrossRefGoogle Scholar
  34. Hildebrand, C., 1971, Ultrastructural and light-microscopic studies of the developing feline spinal cord white matter. II. Cell death and myelin sheath disintegration in the early postnatal period, Acta Physiol. Scand., 364: 109.Google Scholar
  35. Hirano, A., Zimmerman, H. M., and Levine, S., 1966, Myelin in the central nervous system as observed in experimentally induced edema in the rat, J. Cell Biol., 31: 397.CrossRefGoogle Scholar
  36. Israelachvili, J. N., Marcelja, S. and Horn, R. G., 1980, Physical principles of membrane organization, Quart. Rev. Biophys., 13: 121.CrossRefGoogle Scholar
  37. Jenkinson, T. J., Kamat, V. B., and Chapman, D., 1969, Physical studies on myelin II., Biochim. Biophys. Acta, 163: 427.Google Scholar
  38. Kirschner, D. A., Hollingshead, C. J., Thaxton, C., Caspar, D. L. D., and Goodenough, D. A., 1979, Structural states of myelin observed by X-ray diffraction and freeze-fracture electron microscopy, J. Cell Biol., 82: 140.CrossRefGoogle Scholar
  39. Kirschner, D. A. and Ganser, A. L., 1982, Myelin labeled with mercuric chloride: Asymmetric localization of phosphatidylethanolamine plasmalogen, J. Mol. Biol., 157: 635.CrossRefGoogle Scholar
  40. Kirschner, D. A., Ganser, A. L., and Caspar, D. L. D., 1984, Diffraction studies of molecular organisation and membrane interactions in myelin, in: “Myelin”, P. Morell, ed., Plenum Press, New York.Google Scholar
  41. Lampert, P. W., Sims, J. K., and Kniazeff, A. J., 1973, Mechanism of demyelination in JHM virus encephalomyelitis, Acta Neuropathol., Berlin, 24: 76.CrossRefGoogle Scholar
  42. Lampert, P. W., 1978, Autoimmune and virus-induced demyelinating disease, Ann. J. Pathol., 91: 176.Google Scholar
  43. Lampert, P., 1983, Fine Structure of the Demyelinating Process, in: “Multiple Sclerosis. Pathology, diagnosis and management”, J. F. Hallpike, C. W. M. Adams and W. W. Tourtellotte, eds., Chapman & Hall, London.Google Scholar
  44. Lassmann, H., 1983, Comparative Neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis, Springer Verlag, New York.CrossRefGoogle Scholar
  45. Lassmann, H., Sternberger, H., Kitz, K., and Wisniewski, H. M., 1983, In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis, J. Neuro. Sci., 59: 123.CrossRefGoogle Scholar
  46. Laursen, R. A., Samiullah, M., and Lees, M. B., 1984, Structure of bovine brain myelin proteolipid protein and its organisation in myelin, Proc. Natl. Acad. Sci. (U.S.), 81: 2912.CrossRefGoogle Scholar
  47. Lees, M. B., Chao, B., Lin, L. H., Samiullah, M., and Laursen, R., 1983, Amino acid sequence of bovine white matter proteolipid, Arch. Biochim. Biophys., 226: 643.CrossRefGoogle Scholar
  48. Lees, M. B. and Brostoff, S. W., 1984, Proteins of myelin, in: “Myelin”, P. Morell, ed., Plenum Press, New York.Google Scholar
  49. Lin, L-F.H. and Lees, M. B., 1982, Interactions of dicyclohexylcarbodiimide with myelin proteolipid, Proc. Natl. Acad. Sci., 79: 941.CrossRefGoogle Scholar
  50. Linington, C. and Rumsby, M. G., 1980, Accessibility of galactosyl ceramides to probe reagents in central nervous system myelin, J. Neurochem., 35: 983.CrossRefGoogle Scholar
  51. Linington, C. and Rumsby, M. G., 1981, Galactosyl ceramides of the myelin sheath: thermal studies, Neurochem. Int., 3: 211.CrossRefGoogle Scholar
  52. Lofgren, H. and Pascher, I., 1977, Molecular arrangements of sphingolipids. The monolayer behaviour of ceramides, Chem. Phys. Lipids, 20: 273.CrossRefGoogle Scholar
  53. Lohner, K., Hermetter, A., and Paltauf, F., 1984, Phase behaviour of ethanolamine plasmalogen, Chem. Phys. Lip., 34: 163.CrossRefGoogle Scholar
  54. London, Y. and Vossenberg, F. G. A., 1973, Specific interaction of central nervous system myelin basic protein with lipids, Biochim.Biophys. Acta, 307: 478.CrossRefGoogle Scholar
  55. Ludwin, S. K., 1978, Central nervous system demyelination and remyelination in the mouse. An ultrastructural study of cuprizone toxicity, Lab. Invest., 39: 597.Google Scholar
  56. McIntosh, T. J. and Robertson, J. D., 1976, Observations in the effect of hypotonic solutions on the myelin sheath in the central nervous system, J. Mol. Biol., 100: 213.CrossRefGoogle Scholar
  57. Martenson, R. E., 1980, Myelin basic protein: What does it do?, in: “Biochemistry of the Brain”, S. Kumar, ed., Wiley, N.Y.Google Scholar
  58. Mateu, L. and Luzzati, V., 1973, X-ray diffraction and electron microscope study of the interactions of myelin components. The structure of a lamellar phase with a 150 to 180 Å repeat distance containing basic proteins and acidic lipids, J. Mol. Biol., 75: 697.CrossRefGoogle Scholar
  59. Moscarello, M. A., Brady, G. W., Fein, D. B., Wood, D. D., and Cruz, T. F., 1986, The role of charge microheterogeneity of basic protein in the formation and maintenance of the multilayered structure of myelin: a possible role in multiple sclerosis, J. Neurosci. Res., 15: 87.CrossRefGoogle Scholar
  60. Norton, W. T. and Poduslo, S. E., 1973, Myelination in rat brain: changes in myelin composition during brain maturation, J. Neurochem., 21: 759.CrossRefGoogle Scholar
  61. Oldfield, E. and Chapman, D., 1972, Molecular dynamics of cerebroside-cholesterol and sphingomyelin-cholesterol interactions: implications for myelin membrane structure, FEBS letters., 21: 303.CrossRefGoogle Scholar
  62. Omlin, F. X., Webster, H. de F., Palkovits, C. G., and Cohen, S. R., 1982, Immunocytochemical localization of basic protein in major dense line regions of central and peripheral myelin, J. Cell Biol., 95: 242.CrossRefGoogle Scholar
  63. Oxberry, J. M. and Gregson, N. A., 1974, The agglutination of myelin suspensions by specific antisera, Brain Res., 78: 303.CrossRefGoogle Scholar
  64. Papahadjopoulos, D., Moscarello, M., Eylar, E. H. and Isac, T., 1975, Effects of proteins on thermotropic phase transitions of phospholipids membranes, BiochiM. Biophys. Acta, 401: 317.CrossRefGoogle Scholar
  65. Pascher, I., 1976, Molecular arrangements in sphingolipids. Conformation and hydrogen bonding of ceramide and their implication on membrane stability and permeability, Biochim. Biophys. Acta, 455: 433.CrossRefGoogle Scholar
  66. Pascher, I. and Sundell, S., 1977, Molecular arrangements in sphingolipids. The crystal structure of cerebroside, Chem. Phys. Lipids, 20: 175.CrossRefGoogle Scholar
  67. Peters, A., Sandford, L. P., and Webster, H. de F., 1976, The fine structure of the nervous system, Harper and Row, London.Google Scholar
  68. Poduslo, J. F. and Braun, P. E., 1975, Topographical arrangement of membrane proteins in the intact myelin sheath, J. Biol. Chem., 250: 1099.Google Scholar
  69. Pritchett, S. M., 1980, M. Phil thesis, University of York.Google Scholar
  70. Quarles, R. H., 1984, Myelin-associated glycoprotein in development and disease, Dev. Neurosci., 6: 285.CrossRefGoogle Scholar
  71. Raff, M. C., Mirsky, R., Fields, K. L., Lisak, R. P., Dorfman, S. H., Silberberg, D. H., Gregson, N. A., Leibowitz, S., and Kennedy, M. C., 1978, Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture, Nature, 274: 813.Google Scholar
  72. Raff, M. C., Miller, R. H., and Noble, M., 1983, A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium, Nature, 303: 390.CrossRefGoogle Scholar
  73. Raff, M. C., Abney, Erika, R., and Fok-Seang, J., 1985, Reconstitution of a developmental clock in vitro: a critical role for astrocytes in the timing of oligodendrocyte differentiation, Cell, 42: 61.CrossRefGoogle Scholar
  74. Raine, C. S., Johnson, A. B., Marcus, D. M., Suzuki, A., and Bornstein, M. B., 1981, Demyelination in vitro: Absorption studies demonstrate that galactocerebroside is a major target, J. Neurol. Sci., 52: 117.CrossRefGoogle Scholar
  75. Raine, C. S., 1984, Morphology of myelin and myelination, in: “Myelin”, P. Morell, ed., Plenum Press, New York.Google Scholar
  76. Rand, R. P., Fuller, N. L., and Lis, L. J., 1979, Myelin swelling and measurement of forces between myelin membranes, Nature, 279: 258.CrossRefGoogle Scholar
  77. Reale, E., Luciano, L., and Spitznas, M., 1975, Zonulae occludents of the myelin lamellae in the nerve fibre layer of the retina and in the optic nerve of the rabbit: a demonstration by the freeze-fracture method, J. Neurocytol., 4: 131.CrossRefGoogle Scholar
  78. Reiber, H., Suckling, A. J., and Rumsby, M. G., 1984, The effects of Freund’s adjuvants on blood-cerebrospinal fluid barrier permeability, J. Neurol. Sci., 63: 55.CrossRefGoogle Scholar
  79. Rothman, J. and Lenard, J., 1977, Membrane Asymmetry, Science, 195: 743.CrossRefGoogle Scholar
  80. Rumsby, M. G., 1978, Organization and structure in central-nerve myelin, Biochem. Soc. Trans., 6: 448.Google Scholar
  81. Rumsby, M. G. and Crang, A. J., 1977, The myelin sheath a structural examination, in: “The Synthesis, Assembly and Turnover of Cell Surface Components, G. Poste and G. L. Nicolson, eds., Noth Holland Pub. Co., Amsterdam.Google Scholar
  82. Rumsby, M. G. and Fish, L. J., 1980, Hypotonic swelling and the structure of myelin lamellae in the central nervous system of normal and jimpy, quaking and shiverer mutant mice; the radial component of myelin, in: “Neurological Mutations Affecting Myelination”, N. Baumann, ed., North-Holland Biomedical Press.Google Scholar
  83. Ruocco, M. J. and Shipley, G. G., 1984, Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes, Biophys. J., 46: 695.CrossRefGoogle Scholar
  84. Sato, S., Quarles, R. H., and Bradby, R. 0., 1982, Susceptibility of the myelin-associated glycoprotein and basic protein to a neutral protease in highly purified myelin from human and rat brain, J. Neurochem., 39: 97.CrossRefGoogle Scholar
  85. Schmidt, Q. F., Barenholz, Y., Huang, C., and Thompson, T. E., 1978, Monolayer coupling in sphingomyelin bilayer systems, Nature, 271: 775.CrossRefGoogle Scholar
  86. Sedzik, J., Blaurock, A. E., and Hochli, M., 1984, Lipid/myelin basic protein multilayers. A model for the cytoplasmic space in central nervous system myelin, J. Mol. Biol., 174: 385.CrossRefGoogle Scholar
  87. Singer, S. J. and Nicholson, G. L., 1972, The fluid mosaic model of the structure of cell membranes, Science, 175: 720.CrossRefGoogle Scholar
  88. Smith, R., 1977, Non-covalent cross-linking of lipid bilayers by myelin basic protein: a possible role in myelin formation, Biochim. Biophys. Acta, 470: 170.CrossRefGoogle Scholar
  89. Smith, R. and MacDonald, B. J., 1979, Association of myelin basic protein with detergent micelles, Biochim. Biophys. Acta, 554: 133.CrossRefGoogle Scholar
  90. Smith, K. J., Hall, S. M., and Schauf, C. L., 1985, Vesicular demyelination induced by raised intracellular calcium, J. Neurol. Sci., 71: 19.CrossRefGoogle Scholar
  91. Stoffel, W., Hillen, H., Schroeder, W., and Deutzman, R., 1983, The primary structure of bovine brain myelin lipophilin (proteolipid apoprotein). Hoppe-Seyler’s Z. Physiol. Chem., 364: 1455.CrossRefGoogle Scholar
  92. Suzumura, A., Silberberg, D. H., and Lisak, R. P., 1986, The expression of MHC antigens on oligodendrocytes: induction of polymorphic H-2 expression by limphokines, J. Neuroommunol., 11: 179.CrossRefGoogle Scholar
  93. Tabira, T., Cullen, M. J., Reier, P. J., and de F Webster, H., 1978, An experimental analysis of interlamellar tight junctions in amphibian and mammalian CNS myelin, J. Neurocytol., 7: 489.CrossRefGoogle Scholar
  94. Townsend, A. R. M., Gotch, F. M., and Davey, J., 1985, Cytotoxic T cells recognize fragments of the influenza nucleoprotein, Cell, 42: 457.CrossRefGoogle Scholar
  95. Vanguri, P., Koski, C. L., Silverman, B., and Shin, M. L., 1982, Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies, Proc. Natl. Acad. Sci., 79: 3290.CrossRefGoogle Scholar
  96. Walker, A. G., and Rumsby, M. G., 1985, The induction of liposome aggregation by myelin basic protein, Neurochem. Int., 74: 441.CrossRefGoogle Scholar
  97. Walker, A. G., Chapman, J. A., and Rumsby, M. G., 1985, Immunocytochemical demonstration of glial-neuronal interactions and myelinogenesis in subcultures of rat brain cells, J. Neuroimmunol., 9: 159.CrossRefGoogle Scholar
  98. Webster, H. de F., Shii, H., and Lassmann, H., 1983, Immunocytochemical study of myelin-associated glycoprotein (MAG), Basic protein and glial fibrillary acidic protein (GFAP) in chronic relapsing experimental allergic encephalomyelitis, Acta Neuropath., 65: 177.CrossRefGoogle Scholar
  99. Wong, G. H. W., Bartlett, P. F., Clark-Lewis, I., Battye, F., and Schrader, J. W., 1984, Inducible expression of H-2 and Ia antigens on brain cells, Nature, 310: 23.CrossRefGoogle Scholar
  100. Wood, P. M. and Williams, A. K., 1984, Oligodendrocyte proliferation and CNS myelination in cultures containding dissociated embryonic neuroglia and dorsal root ganglion neurons, Dev. Brain. Res., 12: 225.CrossRefGoogle Scholar
  101. Wood, D. D. and Moscarello, M. A., 1984, Is the myelin membrane abnormal in Multiple Sclerosis?, J. Memb. Biol., 79: 195.CrossRefGoogle Scholar
  102. Young, P. R., Vacante, D. A., and Snyder, W. R., 1982, Protein-induced aggregation of lipid vesicles. Mechanism of the myelin basic proteinmyelin interaction, J. Am. Chem. Soc., 104: 7287.CrossRefGoogle Scholar
  103. Young, J. D-E. and Cohn, Z. A., 1986, Cell-mediated killing: a common mechanism?, 1986, Cell, 46: 641.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • M. G. Rumsby
    • 1
  1. 1.Department of BiologyUniversity of YorkYorkEngland

Personalised recommendations