Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1984 Aug 1;99(2):594–606. doi: 10.1083/jcb.99.2.594

Immunocytochemical studies of quaking mice support a role for the myelin-associated glycoprotein in forming and maintaining the periaxonal space and periaxonal cytoplasmic collar of myelinating Schwann cells

PMCID: PMC2113285  PMID: 6204994

Abstract

The myelin-associated glycoprotein (MAG) is an integral membrane glycoprotein that is located in the periaxonal membrane of myelin- forming Schwann cells. On the basis of this localization, it has been hypothesized that MAG plays a structural role in (a) forming and maintaining contact between myelinating Schwann cells and the axon (the 12-14-nm periaxonal space) and (b) maintaining the Schwann cell periaxonal cytoplasmic collar of myelinated fibers. To test this hypothesis, we have determined the immunocytochemical localization of MAG in the L4 ventral roots from 11-mo-old quaking mice. These roots display various stages in the association of remyelinating Schwann cells with axons, and abnormalities including loss of the Schwann cell periaxonal cytoplasmic collar and dilation of the periaxonal space of myelinated fibers. Therefore, this mutant provides distinct opportunities to observe the relationships between MAG and (a) the formation of the periaxonal space during remyelination and (b) the maintenance of the periaxonal space and Schwann cell periaxonal cytoplasmic collar in myelinated fibers. During association of remyelinating Schwann cells and axons, MAG was detected in Schwann cell adaxonal membranes that apposed the axolemma by 12-14 nm. Schwann cell plasma membranes separated from the axolemma by distances greater than 12-14 nm did not react with MAG antiserum. MAG was present in adaxonal Schwann cell membranes that apposed the axolemma by 12-14 nm but only partially surrounded the axon and, therefore, may be actively involved in the ensheathment of axons by remyelinating Schwann cells. To test the dual role of MAG in maintaining the periaxonal space and Schwann cell periaxonal cytoplasmic collar of myelinated fibers, we determined the immunocytochemical localization of MAG in myelinated quaking fibers that displayed pathological alterations of these structures. Where Schwann cell periaxonal membranes were not stained by MAG antiserum, the cytoplasmic side of the periaxonal membrane was "fused" with the cytoplasmic side of the inner compact myelin lamella and formed a major dense line. This loss of MAG and the Schwann cell periaxonal cytoplasmic collar usually resulted in enlargement of the 12-14-nm periaxonal space and ruffling of the apposing axolemma. In myelinated fibers, there was a strict correlation between the presence of MAG in the Schwann cell periaxonal membrane and (a) maintenance of the 12-14- nm periaxonal space, and (b) presence of the Schwann cell periaxonal cytoplasmic collar.(ABSTRACT TRUNCATED AT 400 WORDS)

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bunge M. B., Williams A. K., Wood P. M. Neuron-Schwann cell interaction in basal lamina formation. Dev Biol. 1982 Aug;92(2):449–460. doi: 10.1016/0012-1606(82)90190-7. [DOI] [PubMed] [Google Scholar]
  2. Davis J., Bennett V. Brain spectrin. Isolation of subunits and formation of hybrids with erythrocyte spectrin subunits. J Biol Chem. 1983 Jun 25;258(12):7757–7766. [PubMed] [Google Scholar]
  3. Figlewicz D. A., Quarles R. H., Johnson D., Barbarash G. R., Sternberger N. H. Biochemical demonstration of the myelin-associated glycoprotein in the peripheral nervous system. J Neurochem. 1981 Sep;37(3):749–758. doi: 10.1111/j.1471-4159.1982.tb12551.x. [DOI] [PubMed] [Google Scholar]
  4. Geiger B. Membrane-cytoskeleton interaction. Biochim Biophys Acta. 1983 Aug 11;737(3-4):305–341. doi: 10.1016/0304-4157(83)90005-9. [DOI] [PubMed] [Google Scholar]
  5. Glenney J. R., Jr, Glenney P. Fodrin is the general spectrin-like protein found in most cells whereas spectrin and the TW protein have a restricted distribution. Cell. 1983 Sep;34(2):503–512. doi: 10.1016/0092-8674(83)90383-5. [DOI] [PubMed] [Google Scholar]
  6. Hirano A., Dembitzer H. M. The periaxonal space in an experimental model of neuropathy: the mutant Syrian hamster with hindleg paralysis. J Neurocytol. 1981 Apr;10(2):261–269. doi: 10.1007/BF01257971. [DOI] [PubMed] [Google Scholar]
  7. Itoyama Y., Sternberger N. H., Webster H. D., Quarles R. H., Cohen S. R., Richardson E. P., Jr Immunocytochemical observations on the distribution of myelin-associated glycoprotein and myelin basic protein in multiple sclerosis lesions. Ann Neurol. 1980 Feb;7(2):167–177. doi: 10.1002/ana.410070212. [DOI] [PubMed] [Google Scholar]
  8. Itoyama Y., Webster H. D. Immunocytochemical study of myelin-associated glycoprotein (MAG) and basic protein (BP) in acute experimental allergic encephalomyelitis (EAE). J Neuroimmunol. 1982 Dec;3(4):351–364. doi: 10.1016/0165-5728(82)90037-6. [DOI] [PubMed] [Google Scholar]
  9. Johnson D., Quarles R. H., Brady R. O. A radioimmunoassay for the myelin-associated glycoprotein. J Neurochem. 1982 Nov;39(5):1356–1362. doi: 10.1111/j.1471-4159.1982.tb12578.x. [DOI] [PubMed] [Google Scholar]
  10. Kimbrough R. D., Gaines T. B. Hexachlorophene effects on the rat brain: study of high doses by light and electron microscopy. Arch Environ Health. 1971 Aug;23(2):114–118. doi: 10.1080/00039896.1971.10665966. [DOI] [PubMed] [Google Scholar]
  11. Martin J. R., Webster H. D. Mitotic Schwann cells in developing nerve: their changes in shape, fine structure, and axon relationships. Dev Biol. 1973 Jun;32(2):417–431. doi: 10.1016/0012-1606(73)90251-0. [DOI] [PubMed] [Google Scholar]
  12. McIntyre R. J., Quarles R. H., deF Webster H., Brady R. O. Isolation and characterization of myelin-related membranes. J Neurochem. 1978 May;30(5):991–1002. doi: 10.1111/j.1471-4159.1978.tb12391.x. [DOI] [PubMed] [Google Scholar]
  13. Quarles R. H., Barbarash G. R., Figlewicz D. A., McIntyre L. J. Purification and partial characterization of the myelin-associated glycoprotein from adult rat brain. Biochim Biophys Acta. 1983 May 4;757(1):140–143. doi: 10.1016/0304-4165(83)90162-9. [DOI] [PubMed] [Google Scholar]
  14. Sabatini D. D., Kreibich G., Morimoto T., Adesnik M. Mechanisms for the incorporation of proteins in membranes and organelles. J Cell Biol. 1982 Jan;92(1):1–22. doi: 10.1083/jcb.92.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schober R., Itoyama Y., Sternberger N. H., Trapp B. D., Richardson E. P., Asbury A. K., Quarles R. H., Webster H. D. Immunocytochemical study of P0 glycoprotein, P1 and P2 basic proteins, and myelin-associated glycoprotein (MAG) in lesions of idiopathic polyneuritis. Neuropathol Appl Neurobiol. 1981 Nov-Dec;7(6):421–434. doi: 10.1111/j.1365-2990.1981.tb00243.x. [DOI] [PubMed] [Google Scholar]
  16. Sternberger N. H., Quarles R. H., Itoyama Y., Webster H. D. Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1510–1514. doi: 10.1073/pnas.76.3.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Suzuki K., Nagara H. Quaking mouse: vacuolar degeneration of spinal roots. Acta Neuropathol. 1982;58(4):269–274. doi: 10.1007/BF00688608. [DOI] [PubMed] [Google Scholar]
  18. Suzuki K., Zagoren J. C. Quaking mouse: an ultrastructural study of the peripheral nerves. J Neurocytol. 1977 Feb;6(1):71–84. doi: 10.1007/BF01175415. [DOI] [PubMed] [Google Scholar]
  19. Trapp B. D., Quarles R. H., Griffin J. W. Myelin-associated glycoprotein and myelinating Schwann cell-axon interaction in chronic B,B'-iminodipropionitrile neuropathy. J Cell Biol. 1984 Apr;98(4):1272–1278. doi: 10.1083/jcb.98.4.1272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Trapp B. D., Quarles R. H. Immunocytochemical localization of the myelin-associated glycoprotein. Fact or artifact? J Neuroimmunol. 1984 Jul;6(4):231–249. doi: 10.1016/0165-5728(84)90011-0. [DOI] [PubMed] [Google Scholar]
  21. Trapp B. D., Quarles R. H. Presence of the myelin-associated glycoprotein correlates with alterations in the periodicity of peripheral myelin. J Cell Biol. 1982 Mar;92(3):877–882. doi: 10.1083/jcb.92.3.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Webster H. D., Martin R., O'Connell M. F. The relationships between interphase Schwann cells and axons before myelination: a quantitative electron microscopic study. Dev Biol. 1973 Jun;32(2):401–416. doi: 10.1016/0012-1606(73)90250-9. [DOI] [PubMed] [Google Scholar]
  23. Webster H. D., Palkovits C. G., Stoner G. L., Favilla J. T., Frail D. E., Braun P. E. Myelin-associated glycoprotein: electron microscopic immunocytochemical localization in compact developing and adult central nervous system myelin. J Neurochem. 1983 Nov;41(5):1469–1479. doi: 10.1111/j.1471-4159.1983.tb00847.x. [DOI] [PubMed] [Google Scholar]
  24. Winchell K. H., Sternberger N. H., Webster H. D. Myelin-associated glycoprotein localized immunocytochemically in periaxonal regions of oligodendroglia during hexachlorophene intoxication. Brain Res. 1982 May 13;239(2):679–684. doi: 10.1016/0006-8993(82)90550-9. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES