Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Jul 1;111(1):209–215. doi: 10.1083/jcb.111.1.209

Regulation of immunoreactive GAP-43 expression in rat cortical macroglia is cell type specific

PMCID: PMC2116173  PMID: 2142162

Abstract

Growth-associated protein 43 (GAP-43) is an abundant, intensely investigated membrane phosphoprotein of the nervous system (Benowitz, L.I., and A. Routtenberg. 1987. Trends Neurosci. 10:527-532; Skene, J. H. P. 1989. Annu. Rev. Neurosci. 12:127-156), with a hitherto unknown function. We have previously demonstrated that astrocytes, brain macroglial cells, contain GAP-43 (Steisslinger, H. W., V. J. Aloyo, and L. Vitkovic, 1987. Brain Res. 415:375-379; Vitkovic, L., H. W. Steisslinger, V. J. Aloyo, and M. Mersel. 1988. Proc. Natl. Acad. Sci. USA. 85:8296-8300; Vitkovic L., and M. Mersel. 1989. Metab. Brain Dis. 4:47-53). Results from double immunofluorescent labeling experiments presented here show that oligodendrocytes also contain GAP-43 immunoreactivity (GAP-43ir). Thus, all three macroglial cell types of the central nervous system (type I and type 2 astrocytes and oligodendrocytes) contain GAP-43. Whereas immunoreactive GAP-43 is expressed by progenitors of all macroglial cell types, the developmental regulation of its expression is cell type specific. Immunoreactive GAP-43 is downregulated in type 1 astrocytes, and constitutively expressed in both type 2 astrocytes and oligodendrocytes. These results may be relevant to potential function(s) of GAP-43.

Full Text

The Full Text of this article is available as a PDF (3.5 MB).

Selected References

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

  1. Abney E. R., Bartlett P. P., Raff M. C. Astrocytes, ependymal cells, and oligodendrocytes develop on schedule in dissociated cell cultures of embryonic rat brain. Dev Biol. 1981 Apr 30;83(2):301–310. doi: 10.1016/0012-1606(81)90476-0. [DOI] [PubMed] [Google Scholar]
  2. Bartlett P. F., Noble M. D., Pruss R. M., Raff M. C., Rattray S., Williams C. A. Rat neural antigen-2 (RAN-2): a cell surface antigen on astrocytes, ependymal cells, Müller cells and lepto-meninges defined by a monoclonal antibody. Brain Res. 1981 Jan 12;204(2):339–351. doi: 10.1016/0006-8993(81)90593-x. [DOI] [PubMed] [Google Scholar]
  3. Basi G. S., Jacobson R. D., Virág I., Schilling J., Skene J. H. Primary structure and transcriptional regulation of GAP-43, a protein associated with nerve growth. Cell. 1987 Jun 19;49(6):785–791. doi: 10.1016/0092-8674(87)90616-7. [DOI] [PubMed] [Google Scholar]
  4. Benowitz L. I., Apostolides P. J., Perrone-Bizzozero N., Finklestein S. P., Zwiers H. Anatomical distribution of the growth-associated protein GAP-43/B-50 in the adult rat brain. J Neurosci. 1988 Jan;8(1):339–352. doi: 10.1523/JNEUROSCI.08-01-00339.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bignami A., Eng L. F., Dahl D., Uyeda C. T. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 1972 Aug 25;43(2):429–435. doi: 10.1016/0006-8993(72)90398-8. [DOI] [PubMed] [Google Scholar]
  6. Dubois-Dalcq M., Behar T., Hudson L., Lazzarini R. A. Emergence of three myelin proteins in oligodendrocytes cultured without neurons. J Cell Biol. 1986 Feb;102(2):384–392. doi: 10.1083/jcb.102.2.384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eccleston P. A., Silberberg D. H. The differentiation of oligodendrocytes in a serum-free hormone-supplemented medium. Brain Res. 1984 Sep;318(1):1–9. doi: 10.1016/0165-3806(84)90056-7. [DOI] [PubMed] [Google Scholar]
  8. Eisenbarth G. S., Walsh F. S., Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913–4917. doi: 10.1073/pnas.76.10.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goslin K., Schreyer D. J., Skene J. H., Banker G. Development of neuronal polarity: GAP-43 distinguishes axonal from dendritic growth cones. Nature. 1988 Dec 15;336(6200):672–674. doi: 10.1038/336672a0. [DOI] [PubMed] [Google Scholar]
  10. Jacobson R. D., Virág I., Skene J. H. A protein associated with axon growth, GAP-43, is widely distributed and developmentally regulated in rat CNS. J Neurosci. 1986 Jun;6(6):1843–1855. doi: 10.1523/JNEUROSCI.06-06-01843.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Karns L. R., Ng S. C., Freeman J. A., Fishman M. C. Cloning of complementary DNA for GAP-43, a neuronal growth-related protein. Science. 1987 May 1;236(4801):597–600. doi: 10.1126/science.2437653. [DOI] [PubMed] [Google Scholar]
  12. Meiri K. F., Pfenninger K. H., Willard M. B. Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci U S A. 1986 May;83(10):3537–3541. doi: 10.1073/pnas.83.10.3537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Miller R. H., Ffrench-Constant C., Raff M. C. The macroglial cells of the rat optic nerve. Annu Rev Neurosci. 1989;12:517–534. doi: 10.1146/annurev.ne.12.030189.002505. [DOI] [PubMed] [Google Scholar]
  14. Miller R. H., Raff M. C. Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct. J Neurosci. 1984 Feb;4(2):585–592. doi: 10.1523/JNEUROSCI.04-02-00585.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Neve R. L., Perrone-Bizzozero N. I., Finklestein S., Zwiers H., Bird E., Kurnit D. M., Benowitz L. I. The neuronal growth-associated protein GAP-43 (B-50, F1): neuronal specificity, developmental regulation and regional distribution of the human and rat mRNAs. Brain Res. 1987 Jul;388(2):177–183. doi: 10.1016/s0006-8993(87)80012-4. [DOI] [PubMed] [Google Scholar]
  16. Novelli A., Reilly J. A., Lysko P. G., Henneberry R. C. Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res. 1988 Jun 7;451(1-2):205–212. doi: 10.1016/0006-8993(88)90765-2. [DOI] [PubMed] [Google Scholar]
  17. Oestreicher A. B., Dekker L. V., Gispen W. H. A radioimmunoassay for the phosphoprotein B-50: distribution in rat brain. J Neurochem. 1986 May;46(5):1366–1369. doi: 10.1111/j.1471-4159.1986.tb01748.x. [DOI] [PubMed] [Google Scholar]
  18. Oestreicher A. B., Van Dongen C. J., Zwiers H., Gispen W. H. Affinity-purified anti-B-50 protein antibody: interference with the function of the phosphoprotein B-50 in synaptic plasma membranes. J Neurochem. 1983 Aug;41(2):331–340. doi: 10.1111/j.1471-4159.1983.tb04747.x. [DOI] [PubMed] [Google Scholar]
  19. Raff M. C., Abney E. R., Cohen J., Lindsay R., Noble M. Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics. J Neurosci. 1983 Jun;3(6):1289–1300. doi: 10.1523/JNEUROSCI.03-06-01289.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Raff M. C., Fields K. L., Hakomori S. I., Mirsky R., Pruss R. M., Winter J. Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. Brain Res. 1979 Oct 5;174(2):283–308. doi: 10.1016/0006-8993(79)90851-5. [DOI] [PubMed] [Google Scholar]
  21. Raff M. C., Mirsky R., Fields K. L., Lisak R. P., Dorfman S. H., Silberberg D. H., Gregson N. A., Leibowitz S., Kennedy M. C. Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture. Nature. 1978 Aug 24;274(5673):813–816. [PubMed] [Google Scholar]
  22. Ranscht B., Clapshaw P. A., Price J., Noble M., Seifert W. Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2709–2713. doi: 10.1073/pnas.79.8.2709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sensenbrenner M., Devilliers G., Bock E., Porte A. Biochemical and ultrastructural studies of cultured rat astroglial cells: effect of brain extract and dibutyryl cyclic AMP on glial fibrillary acidic protein and glial filaments. Differentiation. 1980;17(1):51–61. doi: 10.1111/j.1432-0436.1980.tb01081.x. [DOI] [PubMed] [Google Scholar]
  24. Skene J. H. Axonal growth-associated proteins. Annu Rev Neurosci. 1989;12:127–156. doi: 10.1146/annurev.ne.12.030189.001015. [DOI] [PubMed] [Google Scholar]
  25. Skene J. H., Jacobson R. D., Snipes G. J., McGuire C. B., Norden J. J., Freeman J. A. A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes. Science. 1986 Aug 15;233(4765):783–786. doi: 10.1126/science.3738509. [DOI] [PubMed] [Google Scholar]
  26. Snipes G. J., Chan S. Y., McGuire C. B., Costello B. R., Norden J. J., Freeman J. A., Routtenberg A. Evidence for the coidentification of GAP-43, a growth-associated protein, and F1, a plasticity-associated protein. J Neurosci. 1987 Dec;7(12):4066–4075. doi: 10.1523/JNEUROSCI.07-12-04066.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steisslinger H. W., Aloyo V. J., Vitković L. Characterization of two plasma membrane proteins abundant in rat brain. Brain Res. 1987 Jul 14;415(2):375–379. doi: 10.1016/0006-8993(87)90224-1. [DOI] [PubMed] [Google Scholar]
  28. Temple S., Raff M. C. Differentiation of a bipotential glial progenitor cell in a single cell microculture. Nature. 1985 Jan 17;313(5999):223–225. doi: 10.1038/313223a0. [DOI] [PubMed] [Google Scholar]
  29. Vitković L., Mersel M. Growth-associated protein 43 is down-regulated in cultured astrocytes. Metab Brain Dis. 1989 Mar;4(1):47–53. doi: 10.1007/BF00999493. [DOI] [PubMed] [Google Scholar]
  30. Vitković L., Steisslinger H. W., Aloyo V. J., Mersel M. The 43-kDa neuronal growth-associated protein (GAP-43) is present in plasma membranes of rat astrocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8296–8300. doi: 10.1073/pnas.85.21.8296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Williams B. P., Abney E. R., Raff M. C. Macroglial cell development in embryonic rat brain: studies using monoclonal antibodies, fluorescence activated cell sorting, and cell culture. Dev Biol. 1985 Nov;112(1):126–134. doi: 10.1016/0012-1606(85)90126-5. [DOI] [PubMed] [Google Scholar]
  32. Wolswijk G., Noble M. Identification of an adult-specific glial progenitor cell. Development. 1989 Feb;105(2):387–400. doi: 10.1242/dev.105.2.387. [DOI] [PubMed] [Google Scholar]
  33. Woolf C. J., Reynolds M. L., Molander C., O'Brien C., Lindsay R. M., Benowitz L. I. The growth-associated protein GAP-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury. Neuroscience. 1990;34(2):465–478. doi: 10.1016/0306-4522(90)90155-w. [DOI] [PubMed] [Google Scholar]
  34. Zuber M. X., Goodman D. W., Karns L. R., Fishman M. C. The neuronal growth-associated protein GAP-43 induces filopodia in non-neuronal cells. Science. 1989 Jun 9;244(4909):1193–1195. doi: 10.1126/science.2658062. [DOI] [PubMed] [Google Scholar]

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

RESOURCES