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Gene Review

GAP43  -  growth associated protein 43

Homo sapiens

Synonyms: Axonal membrane protein GAP-43, B-50, Growth-associated protein 43, Neural phosphoprotein B-50, Neuromodulin, ...
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Disease relevance of GAP43


Psychiatry related information on GAP43


High impact information on GAP43

  • We demonstrate here that transection of the mature axons of CA3 pyramidal cells in hippocampal slice cultures leads to the formation by CA3 pyramidal cells of new axon collaterals that are immunoreactive with the growth-associated protein GAP-43 [9].
  • One of the most prominent proteins in the growth-cone membrane is GAP-43 [10].
  • To analyze the sprouting response in AD cortex, we compared the patterns of GAP-43 with synaptophysin immunoreactivity [11].
  • The AD neocortex was characterized by an overall decrease in GAP-43 immunoreactivity accompanied by sprouting neurites in the areas of synaptic pathology [11].
  • We conclude that GAP-43 might be involved in the mechanisms of synaptic plasticity in the AD cortex, as well as in the process of aberrant sprouting in the neuritic plaques [11].

Chemical compound and disease context of GAP43


Biological context of GAP43

  • I have also reported that dysmorphic large neurons also have enhanced gene expression of growth-associated protein GAP43, which is a phosphoprotein enriched at presynaptic nerve terminals and is thought to be involved in axonal outgrowth and plasticity in synaptic connections [17].
  • Taken altogether, these data suggest that the integrity of lipid rafts is necessary for PKC to affect GAP43 and catalyze its phosphorylation [18].
  • We demonstrate that GAP-43 regulates endocytosis and synaptic vesicle recycling [19].
  • Our findings imply that neuronal plasticity as indexed by growth-associated protein-43 expression is impaired, and perhaps aberrantly regulated, in schizophrenia [20].
  • The Mabs NM2 and NM3 cross-react with bovine B-50 immunoreactive c-kinase substrate (BICKS), a protein sharing a 17 amino acid sequence homology with B-50 [21].

Anatomical context of GAP43

  • The osmosensitivity of GAP43 furnishes a mechanistic framework that links axon elongation with phospho inositide metabolism, spontaneous triggering of cytosolic Ca(2+) transients and the regulation of actin dynamics and motility at the growth cone in response to temporal and local mechanical forces [22].
  • Contact with astroglial membranes induces axonal and dendritic growth of human CNS model neurons and affects the distribution of the growth-associated proteins MAP1B and GAP43 [23].
  • OBJECTIVE: To evaluate GAP43 in human olfactory bulb in normal controls and in individuals receiving treatment for neoplasms [1].
  • B-50 immunoreactivity in the different sub-areas of the hippocampus was quantified by image analysis [24].
  • Recently it was reported that B-50 plays a role in the growth morphology of regenerating muscle fibers [2].

Associations of GAP43 with chemical compounds

  • GAP43 stimulates inositol trisphosphate-mediated calcium release in response to hypotonicity [22].
  • Notably, hypotonicity promoted the selective association of GAP43 with the PLC-delta(1) isoform, and a concomitant increase in inositol-1,4,5-trisphosphate (IP(3)) formation [22].
  • Moreover, this location has interesting implications for membrane curvature and local surface pressure effects and may be relevant to a wide variety of other proteins with basic-aromatic clusters, such as phospholipase D, GAP43, SCAMP2, and the N-methyl-d-aspartate receptor [25].
  • After activation of protein kinase C (PKC) with phorbol esters (PMA) or glutamate, the content of PKC and of proteins highly enriched (GAP43, Fyn, and PrP(c)) or not (MARCKS) in DRM was followed [18].
  • Noteworthy was that, after cell treatment with the lipid raft-disrupting drug methyl-beta-cyclodextrin, PKC activation occurred normally, followed by MARCKS phosphorylation, but GAP43 phosphorylation did not occur [18].

Physical interactions of GAP43


Co-localisations of GAP43

  • Calcitonin gene-related peptide and GAP43 immunoreactivity significantly increased and co-localized in cervicothoracic dorsal horn laminae I-III following C17.2 and C17.2/GDNF transplantation [27].

Regulatory relationships of GAP43


Other interactions of GAP43

  • Glial fibrillary acidic protein and B-50 showed no immunoreactivity [32].
  • Sprouting neuritic components of plaques are immunopositive with other growth-associated proteins, such as GAP43, MARCKS, and spectrin [33].
  • CNTF also induced increased levels of the transcript for the growth cone associated protein GAP43 in SK-N-BE, but not in SY5Y cells [34].
  • RESULTS: We observed a significantly lower density of p75NGFR basal cells (37%) in schizophrenia and increases in GAP43 + postmitotic immature neurons (316%) and ratios of GAP43 + postmitotic immature neurons to p75NGFR + cells (665%) and olfactory marker protein + mature neurons to p75NGFR + basal cells (328%) [35].
  • Further, a difference in the degree of allodynia was noted between C17.2- and C17.2/GDNF transplant-treated groups; this difference correlated with the level of CGRP/GAP43 immunoreactivity and sprouting observed in the cervicothoracic dorsal horns [27].

Analytical, diagnostic and therapeutic context of GAP43


  1. Cancer treatment and growth cone-associated protein in human olfactory bulb glomeruli. Struble, R.G., Ghobrial, M. Arch. Otolaryngol. Head Neck Surg. (1998) [Pubmed]
  2. Light microscopy study of low-affinity nerve growth factor receptor and phosphoprotein B-50/neuromodulin in inflammatory myopathies. Heuss, D. Acta Neuropathol. (1996) [Pubmed]
  3. Glial remodeling and neural plasticity in human retinal detachment with proliferative vitreoretinopathy. Sethi, C.S., Lewis, G.P., Fisher, S.K., Leitner, W.P., Mann, D.L., Luthert, P.J., Charteris, D.G. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  4. Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats. Iwata, M., Shirayama, Y., Ishida, H., Kawahara, R. Neuroscience (2006) [Pubmed]
  5. GAP-43 mRNA expression in early development of human nervous system. Kanazir, S., Ruzdijic, S., Vukosavic, S., Ivkovic, S., Milosevic, A., Zecevic, N., Rakic, L. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  6. Growth-associated protein 43 (GAP-43) and synaptophysin alterations in the dentate gyrus of patients with schizophrenia. Chambers, J.S., Thomas, D., Saland, L., Neve, R.L., Perrone-Bizzozero, N.I. Prog. Neuropsychopharmacol. Biol. Psychiatry (2005) [Pubmed]
  7. Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Eastwood, S.L., Harrison, P.J. Brain Res. Bull. (2001) [Pubmed]
  8. Aberrant GAP-43 gene expression in Alzheimer's disease. de la Monte, S.M., Ng, S.C., Hsu, D.W. Am. J. Pathol. (1995) [Pubmed]
  9. Lesion-induced axonal sprouting and hyperexcitability in the hippocampus in vitro: implications for the genesis of posttraumatic epilepsy. McKinney, R.A., Debanne, D., Gähwiler, B.H., Thompson, S.M. Nat. Med. (1997) [Pubmed]
  10. A membrane-targeting signal in the amino terminus of the neuronal protein GAP-43. Zuber, M.X., Strittmatter, S.M., Fishman, M.C. Nature (1989) [Pubmed]
  11. Patterns of aberrant sprouting in Alzheimer's disease. Masliah, E., Mallory, M., Hansen, L., Alford, M., Albright, T., DeTeresa, R., Terry, R., Baudier, J., Saitoh, T. Neuron (1991) [Pubmed]
  12. Mouse glioma gene expression profiling identifies novel human glioma-associated genes. Gutmann, D.H., Huang, Z.Y., Hedrick, N.M., Ding, H., Guha, A., Watson, M.A. Ann. Neurol. (2002) [Pubmed]
  13. Association of GAP-43 with detergent-resistant membranes requires two palmitoylated cysteine residues. Arni, S., Keilbaugh, S.A., Ostermeyer, A.G., Brown, D.A. J. Biol. Chem. (1998) [Pubmed]
  14. Quantitative comparison of growth-associated protein-43 and substance P in ulcerative colitis. Vento, P., Kiviluoto, T., Keränen, U., Järvinen, H.J., Kivilaakso, E., Soinila, S. J. Histochem. Cytochem. (2001) [Pubmed]
  15. In vivo spontaneous neuronal to neuroendocrine lineage conversion in a subset of neuroblastomas. Gestblom, C., Hoehner, J.C., Hedborg, F., Sandstedt, B., Påhlman, S. Am. J. Pathol. (1997) [Pubmed]
  16. Glutamic acid decarboxylase and gamma-aminobutyric acid in Huntington's disease fibroblasts and other cultured cells, determined by a [3H]muscimol radioreceptor assay. Hamel, E., Goetz, I.E., Roberts, E. J. Neurochem. (1981) [Pubmed]
  17. Activated remodeling and N-methyl-D-aspartate (NMDA) receptors in cortical dysplasia. Yamanouchi, H. J. Child Neurol. (2005) [Pubmed]
  18. Changes in the composition of detergent-resistant membrane domains of cultured neurons following protein kinase C activation. Botto, L., Masserini, M., Palestini, P. J. Neurosci. Res. (2007) [Pubmed]
  19. The neuronal growth-associated protein GAP-43 interacts with rabaptin-5 and participates in endocytosis. Neve, R.L., Coopersmith, R., McPhie, D.L., Santeufemio, C., Pratt, K.G., Murphy, C.J., Lynn, S.D. J. Neurosci. (1998) [Pubmed]
  20. Hippocampal and cortical growth-associated protein-43 messenger RNA in schizophrenia. Eastwood, S.L., Harrison, P.J. Neuroscience (1998) [Pubmed]
  21. Immunocytochemical detection of the growth-associated protein B-50 by newly characterized monoclonal antibodies in human brain and muscle. Mercken, M., Lübke, U., Vandermeeren, M., Gheuens, J., Oestreicher, A.B. J. Neurobiol. (1992) [Pubmed]
  22. GAP43 stimulates inositol trisphosphate-mediated calcium release in response to hypotonicity. Caprini, M., Gomis, A., Cabedo, H., Planells-Cases, R., Belmonte, C., Viana, F., Ferrer-Montiel, A. EMBO J. (2003) [Pubmed]
  23. Contact with astroglial membranes induces axonal and dendritic growth of human CNS model neurons and affects the distribution of the growth-associated proteins MAP1B and GAP43. Piontek, J., Régnier-Vigouroux, A., Brandt, R. J. Neurosci. Res. (2002) [Pubmed]
  24. Immunohistochemical characterization of mossy fibre sprouting in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Proper, E.A., Oestreicher, A.B., Jansen, G.H., Veelen, C.W., van Rijen, P.C., Gispen, W.H., de Graan, P.N. Brain (2000) [Pubmed]
  25. Binding of peptides with basic and aromatic residues to bilayer membranes: phenylalanine in the myristoylated alanine-rich C kinase substrate effector domain penetrates into the hydrophobic core of the bilayer. Zhang, W., Crocker, E., McLaughlin, S., Smith, S.O. J. Biol. Chem. (2003) [Pubmed]
  26. Caldesmon-phospholipid interaction. Effect of protein kinase C phosphorylation and sequence similarity with other phospholipid-binding proteins. Vorotnikov, A.V., Bogatcheva, N.V., Gusev, N.B. Biochem. J. (1992) [Pubmed]
  27. Pain with no gain: Allodynia following neural stem cell transplantation in spinal cord injury. Macias, M.Y., Syring, M.B., Pizzi, M.A., Crowe, M.J., Alexanian, A.R., Kurpad, S.N. Exp. Neurol. (2006) [Pubmed]
  28. Ciliary neurotrophic factor promotes the regrowth capacity but not the survival of intraorbitally axotomized retinal ganglion cells in adult hamsters. Cho, K.S., Chan, P.M., So, K.F., Yip, H.K., Chung, S.K. Neuroscience (1999) [Pubmed]
  29. GAP-43 augments G protein-coupled receptor transduction in Xenopus laevis oocytes. Strittmatter, S.M., Cannon, S.C., Ross, E.M., Higashijima, T., Fishman, M.C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  30. Exocytosis in single chromaffin cells: regulation by a secretory granule-associated Go protein. Vitale, N., Gonon, F., Thiersé, D., Aunis, D., Bader, M.F. Cell. Mol. Neurobiol. (1997) [Pubmed]
  31. Acute sublethal global hypoxia induces transient increase of GAP-43 immunoreactivity in the striatum of neonatal rats. Valdez, S.R., Patterson, S.I., Ezquer, M.E., Torrecilla, M., Lama, M.C., Seltzer, A.M. Synapse (2007) [Pubmed]
  32. Expression in the placenta of neuronal markers for perinatal brain damage. Wijnberger, L.D., Nikkels, P.G., van Dongen, A.J., Noorlander, C.W., Mulder, E.J., Schrama, L.H., Visser, G.H. Pediatr. Res. (2002) [Pubmed]
  33. Hyperactivation of signal transduction systems in Alzheimer's disease. Saitoh, T., Horsburgh, K., Masliah, E. Ann. N. Y. Acad. Sci. (1993) [Pubmed]
  34. Ciliary neurotrophic factor-induced gene expression in human neuroblastoma cell lines. Rossino, P., Volpe, G., Negro, A., Callegaro, L., Altruda, F., Tarone, G., Silengo, L. Neurochem. Res. (1995) [Pubmed]
  35. Dysregulation of olfactory receptor neuron lineage in schizophrenia. Arnold, S.E., Han, L.Y., Moberg, P.J., Turetsky, B.I., Gur, R.E., Trojanowski, J.Q., Hahn, C.G. Arch. Gen. Psychiatry (2001) [Pubmed]
  36. Expression and distribution of GAP-43 in human astrocytes in culture. Moretto, G., Xu, R.Y., Monaco, S., Rizzuto, N., Kim, S.U. Neuropathol. Appl. Neurobiol. (1995) [Pubmed]
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