Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1988 Apr 1;106(4):1281–1288. doi: 10.1083/jcb.106.4.1281

Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading

PMCID: PMC2115009  PMID: 3360853

Abstract

Lack of neurite growth in optic nerve explants in vitro has been suggested to be due to nonpermissive substrate properties of higher vertebrate central nervous system (CNS) white matter. We have searched for surface components in CNS white matter, which would prevent neurite growth. CNS, but not peripheral nervous system (PNS) myelin fractions from rat and chick were highly nonpermissive substrates in vitro. We have used an in vitro spreading assay with 3T3 cells to quantify substrate qualities of membrane fractions and of isolated membrane proteins reconstituted in artificial lipid vesicles. CNS myelin nonpermissiveness was abolished by treatment with proteases and was not associated with myelin lipid. Nonpermissive proteins were found to be membrane bound and yielded highly nonpermissive substrates upon reconstitution into liposomes. Size fractionation of myelin protein by SDS-PAGE revealed two highly nonpermissive minor protein fractions of Mr 35 and 250-kD. Removal of 35- and of 250-kD protein fractions yielded a CNS myelin protein fraction with permissive substrate properties. Supplementation of permissive membrane protein fractions (PNS, liver) with low amounts of 35- or of 250-kD CNS myelin protein was sufficient to generate highly nonpermissive substrates. Inhibitory 35- and 250-kD proteins were found to be enriched in CNS white matter and were found in optic nerve cell cultures which contained highly nonpermissive, differentiated oligodendrocytes. The data presented demonstrate the existence of membrane proteins with potent nonpermissive substrate properties. Distribution and properties suggest that these proteins might play a crucial inhibitory role during development and regeneration in CNS white matter.

Full Text

The Full Text of this article is available as a PDF (2.4 MB).

Selected References

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

  1. Benfey M., Aguayo A. J. Extensive elongation of axons from rat brain into peripheral nerve grafts. Nature. 1982 Mar 11;296(5853):150–152. doi: 10.1038/296150a0. [DOI] [PubMed] [Google Scholar]
  2. Björklund A., Stenevi U. Intracerebral neural implants: neuronal replacement and reconstruction of damaged circuitries. Annu Rev Neurosci. 1984;7:279–308. doi: 10.1146/annurev.ne.07.030184.001431. [DOI] [PubMed] [Google Scholar]
  3. Bohn R. C., Reier P. J., Sourbeer E. B. Axonal interactions with connective tissue and glial substrata during optic nerve regeneration in Xenopus larvae and adults. Am J Anat. 1982 Dec;165(4):397–419. doi: 10.1002/aja.1001650405. [DOI] [PubMed] [Google Scholar]
  4. Bregman B. S. Spinal cord transplants permit the growth of serotonergic axons across the site of neonatal spinal cord transection. Brain Res. 1987 Aug;431(2):265–279. doi: 10.1016/0165-3806(87)90214-8. [DOI] [PubMed] [Google Scholar]
  5. Brunner J., Hauser H., Semenza G. Single bilayer lipid-protein vesicles formed from phosphatidylcholine and small intestinal sucrase.isomaltase. J Biol Chem. 1978 Oct 25;253(20):7538–7546. [PubMed] [Google Scholar]
  6. Carbonetto S., Evans D., Cochard P. Nerve fiber growth in culture on tissue substrata from central and peripheral nervous systems. J Neurosci. 1987 Feb;7(2):610–620. doi: 10.1523/JNEUROSCI.07-02-00610.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colman D. R., Kreibich G., Frey A. B., Sabatini D. D. Synthesis and incorporation of myelin polypeptides into CNS myelin. J Cell Biol. 1982 Nov;95(2 Pt 1):598–608. doi: 10.1083/jcb.95.2.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Commissiong J. W. Fetal locus coeruleus transplanted into the transected spinal cord of the adult rat: some observations and implications. Neuroscience. 1984 Jul;12(3):839–853. doi: 10.1016/0306-4522(84)90174-x. [DOI] [PubMed] [Google Scholar]
  9. Daniloff J. K., Chuong C. M., Levi G., Edelman G. M. Differential distribution of cell adhesion molecules during histogenesis of the chick nervous system. J Neurosci. 1986 Mar;6(3):739–758. doi: 10.1523/JNEUROSCI.06-03-00739.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Everly J. L., Brady R. O., Quarles R. H. Evidence that the major protein in rat sciatic nerve myelin is a glycoprotein. J Neurochem. 1973 Aug;21(2):329–334. doi: 10.1111/j.1471-4159.1973.tb04253.x. [DOI] [PubMed] [Google Scholar]
  11. Guenther J., Nick H., Monard D. A glia-derived neurite-promoting factor with protease inhibitory activity. EMBO J. 1985 Aug;4(8):1963–1966. doi: 10.1002/j.1460-2075.1985.tb03878.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hopkins J. M., Ford-Holevinski T. S., McCoy J. P., Agranoff B. W. Laminin and optic nerve regeneration in the goldfish. J Neurosci. 1985 Nov;5(11):3030–3038. doi: 10.1523/JNEUROSCI.05-11-03030.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liesi P. Laminin-immunoreactive glia distinguish regenerative adult CNS systems from non-regenerative ones. EMBO J. 1985 Oct;4(10):2505–2511. doi: 10.1002/j.1460-2075.1985.tb03963.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Liuzzi F. J., Lasek R. J. Regeneration of motoneuron axons into the adult frog spinal cord after ventral-to-dorsal-root anastomosis. J Comp Neurol. 1986 May 1;247(1):111–122. doi: 10.1002/cne.902470107. [DOI] [PubMed] [Google Scholar]
  15. Mains R. E., Patterson P. H. Primary cultures of dissociated sympathetic neurons. I. Establishment of long-term growth in culture and studies of differentiated properties. J Cell Biol. 1973 Nov;59(2 Pt 1):329–345. doi: 10.1083/jcb.59.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McConnell P., Berry M. Regeneration of ganglion cell axons in the adult mouse retina. Brain Res. 1982 Jun 10;241(2):362–365. doi: 10.1016/0006-8993(82)91079-4. [DOI] [PubMed] [Google Scholar]
  17. Nornes H., Björklund A., Stenevi U. Reinnervation of the denervated adult spinal cord of rats by intraspinal transplants of embryonic brain stem neurons. Cell Tissue Res. 1983;230(1):15–35. doi: 10.1007/BF00216024. [DOI] [PubMed] [Google Scholar]
  18. Richardson P. M., Issa V. M., Aguayo A. J. Regeneration of long spinal axons in the rat. J Neurocytol. 1984 Feb;13(1):165–182. doi: 10.1007/BF01148324. [DOI] [PubMed] [Google Scholar]
  19. Schaffner W., Weissmann C. A rapid, sensitive, and specific method for the determination of protein in dilute solution. Anal Biochem. 1973 Dec;56(2):502–514. doi: 10.1016/0003-2697(73)90217-0. [DOI] [PubMed] [Google Scholar]
  20. Schwab M. E., Thoenen H. Dissociated neurons regenerate into sciatic but not optic nerve explants in culture irrespective of neurotrophic factors. J Neurosci. 1985 Sep;5(9):2415–2423. doi: 10.1523/JNEUROSCI.05-09-02415.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. So K. F., Aguayo A. J. Lengthy regrowth of cut axons from ganglion cells after peripheral nerve transplantation into the retina of adult rats. Brain Res. 1985 Mar 4;328(2):349–354. doi: 10.1016/0006-8993(85)91047-9. [DOI] [PubMed] [Google Scholar]
  22. Weinberg E. L., Spencer P. S. Studies on the control of myelinogenesis. 3. Signalling of oligodendrocyte myelination by regenerating peripheral axons. Brain Res. 1979 Feb 23;162(2):273–279. doi: 10.1016/0006-8993(79)90289-0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES