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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 May;85(10):3638–3642. doi: 10.1073/pnas.85.10.3638

Growth-associated protein GAP-43 is expressed selectively in associative regions of the adult human brain.

R L Neve 1, E A Finch 1, E D Bird 1, L I Benowitz 1
PMCID: PMC280269  PMID: 3368468

Abstract

GAP-43 is a neuron-specific phosphoprotein that has been linked with the development and functional modulation of synaptic relationships. cDNAs for the human GAP-43 gene were used to reveal high overall levels of GAP-43 mRNA in a number of integrative areas of the neocortex, but low levels in cortical areas involved in the initial processing of sensory information, in several brainstem structures, and in caudate-putamen. Neurons expressing highest levels of GAP-43 mRNA were found by in situ hybridization to be concentrated in layer 2 of association cortex and in hippocampal pyramidal cells. Control studies showed that several other RNAs had regional distributions that were different from GAP-43, although the mRNA encoding the precursor of the Alzheimer amyloid beta protein followed a similar pattern of expression. These results suggest that a restricted subset of cortical and hippocampal neurons may be specialized for synaptic remodeling and might play a role in information storage in the human brain.

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Selected References

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  1. Akers R. F., Routtenberg A. Protein kinase C phosphorylates a 47 Mr protein (F1) directly related to synaptic plasticity. Brain Res. 1985 May 13;334(1):147–151. doi: 10.1016/0006-8993(85)90576-1. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Benowitz L. I., Lewis E. R. Increased transport of 44,000- to 49,000-dalton acidic proteins during regeneration of the goldfish optic nerve: a two-dimensional gel analysis. J Neurosci. 1983 Nov;3(11):2153–2163. doi: 10.1523/JNEUROSCI.03-11-02153.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Gispen W. H., Leunissen J. L., Oestreicher A. B., Verkleij A. J., Zwiers H. Presynaptic localization of B-50 phosphoprotein: the (ACTH)-sensitive protein kinase substrate involved in rat brain polyphosphoinositide metabolism. Brain Res. 1985 Mar 4;328(2):381–385. doi: 10.1016/0006-8993(85)91054-6. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Jolles J., Zwiers H., van Dongen C. J., Schotman P., Wirtz K. W., Gispen W. H. Modulation of brain polyphosphoinositide metabolism by ACTH-sensitive protein phosphorylation. Nature. 1980 Aug 7;286(5773):623–625. doi: 10.1038/286623a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Katz F., Ellis L., Pfenninger K. H. Nerve growth cones isolated from fetal rat brain. III. Calcium-dependent protein phosphorylation. J Neurosci. 1985 Jun;5(6):1402–1411. doi: 10.1523/JNEUROSCI.05-06-01402.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lawrence J. B., Singer R. H. Quantitative analysis of in situ hybridization methods for the detection of actin gene expression. Nucleic Acids Res. 1985 Mar 11;13(5):1777–1799. doi: 10.1093/nar/13.5.1777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lovinger D. M., Akers R. F., Nelson R. B., Barnes C. A., McNaughton B. L., Routtenberg A. A selective increase in phosporylation of protein F1, a protein kinase C substrate, directly related to three day growth of long term synaptic enhancement. Brain Res. 1985 Sep 16;343(1):137–143. doi: 10.1016/0006-8993(85)91167-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Mitani A., Shimokouchi M., Itoh K., Nomura S., Kudo M., Mizuno N. Morphology and laminar organization of electrophysiologically identified neurons in the primary auditory cortex in the cat. J Comp Neurol. 1985 May 22;235(4):430–447. doi: 10.1002/cne.902350403. [DOI] [PubMed] [Google Scholar]
  15. Nelson R. B., Friedman D. P., O'Neill J. B., Mishkin M., Routtenberg A. Gradients of protein kinase C substrate phosphorylation in primate visual system peak in visual memory storage areas. Brain Res. 1987 Jul 28;416(2):387–392. doi: 10.1016/0006-8993(87)90924-3. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Neve R. L., Selkoe D. J., Kurnit D. M., Kosik K. S. A cDNA for a human microtubule associated protein 2 epitope in the Alzheimer neurofibrillary tangle. Brain Res. 1986 Nov;387(2):193–196. doi: 10.1016/0169-328x(86)90011-2. [DOI] [PubMed] [Google Scholar]
  18. Oestreicher A. B., Gispen W. H. Comparison of the immunocytochemical distribution of the phosphoprotein B-50 in the cerebellum and hippocampus of immature and adult rat brain. Brain Res. 1986 Jun 11;375(2):267–279. doi: 10.1016/0006-8993(86)90747-x. [DOI] [PubMed] [Google Scholar]
  19. Perrone-Bizzozero N. I., Finklestein S. P., Benowitz L. I. Synthesis of a growth-associated protein by embryonic rat cerebrocortical neurons in vitro. J Neurosci. 1986 Dec;6(12):3721–3730. doi: 10.1523/JNEUROSCI.06-12-03721.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Skene J. H., Willard M. Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems. J Cell Biol. 1981 Apr;89(1):96–103. doi: 10.1083/jcb.89.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Skene J. H., Willard M. Changes in axonally transported proteins during axon regeneration in toad retinal ganglion cells. J Cell Biol. 1981 Apr;89(1):86–95. doi: 10.1083/jcb.89.1.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A., St George-Hyslop P., Van Keuren M. L., Patterson D., Pagan S., Kurnit D. M., Neve R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880–884. doi: 10.1126/science.2949367. [DOI] [PubMed] [Google Scholar]

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