Alternative titles; symbols
HGNC Approved Gene Symbol: GAP43
Cytogenetic location: 3q13.31 Genomic coordinates (GRCh38): 3:115,623,510-115,721,483 (from NCBI)
GAP43 was first discovered in optic neurons of toads, but proves to be a phylogenetically distributed protein whose mRNA is localized exclusively to nerve tissue where the protein is linked to the synaptosomal membrane. GAP43 is considered to be a crucial component of an effective regenerative response in the nervous system. Its phosphorylation by protein kinase C (176960) correlates with long-term potentiation. Kosik et al. (1988) found a high degree of homology between the sequence of the human gene and the rat gene; this homology extended into the 3-prime untranslated region. Adams et al. (1996) noted that gly-glu-lys-lys-asp, an amino acid motif present in GAP43, is also found in several other growth factor-related proteins: Xenopus embryonic fibroblast growth factor, yeast cell division control protein NDA4, and ependymin, a brain glycoprotein neurotrophic factor contributing to optic nerve regeneration and long-term memory consolidation in one order of teleost fish, Cypriniformes.
De Groen et al. (1995) isolated and characterized exon 1 and the promoter of the human GAP43 gene. They showed that the human GAP43 gene is expressed similarly to the previously characterized rat B-50 gene.
Chen et al. (2003) used cDNA microarrays to measure the expression of multiple genes in primary cultured rat hippocampal cells exposed to 1 mmol/L desipramine, 2 mmol/L tranylcypromine, 1 mmol/L lithium, and 10 mmol/L haloperidol. In situ hybridization revealed that desipramine increased GAP43 gene expression in dentate gyrus but not other brain regions. Northern and immunoblotting analyses showed that GAP43 mRNA and protein levels were increased in response to both desipramine and tranylcypromine but not in response to lithium or haloperidol. Because GAP43 regulates the growth of axons and modulates the formation of new connections, Chen et al. (2003) suggested that desipramine may have an effect on neuronal plasticity in the CNS.
By somatic cell analysis Kosik et al. (1988) localized the GAP43 gene to human chromosome 3 and to mouse chromosome 16. Reeves et al. (1989) determined the interval between the Gap43 and Smst (182450) genes on mouse chromosome 16 by studies in 4 different backcrosses.
GAP43 has been termed a 'growth' or 'plasticity' protein because it is expressed at high levels in neuronal growth cones during development and axonal regeneration. By homologous recombination, Strittmatter et al. (1995) generated mice lacking GAP43. Ninety percent of the mice died in the first 3 weeks of life. In the surviving mice, GAP43-deficient retinal axons remained trapped in the chiasm for 6 days after the adult pattern would normally be established, unable to navigate past this midline decision point. Over the subsequent weeks of life, most GAP43-deficient axons did enter the appropriate tracts, however, and the adult CNS was grossly normal. There was no evidence for interference with nerve growth rate, and cultured neurons extended neurites and growth cones in a fashion indistinguishable from controls. Thus, Strittmatter et al. (1995) concluded that the GAP43 protein is not essential for axonal outgrowth or growth cone formation per se, but is required at certain decision points, such as the optic chiasm. GAP43 may serve to amplify pathfinding signals from the growth cone.
Adams, D. S., Kiyokawa, M., Getman, M. E., Shashoua, V. E. Genes encoding giant danio and golden shiner ependymin. Neurochem. Res. 21: 377-384, 1996. [PubMed: 9139245] [Full Text: https://doi.org/10.1007/BF02531655]
Chen, B., Wang, J.-F., Sun, X., Young, L. T. Regulation of GAP-43 expression by chronic desipramine treatment in rat cultured hippocampal cells. Biol. Psychiat. 53: 530-537, 2003. [PubMed: 12644358] [Full Text: https://doi.org/10.1016/s0006-3223(02)01551-2]
de Groen, P. C., Eggen, B. J. L., Gispen, W. H., Schotman, P., Schrama, L. H. Cloning and promoter analysis of the human B-50/GAP-43 gene. J. Molec. Neurosci. 6: 109-119, 1995. [PubMed: 8746449] [Full Text: https://doi.org/10.1007/BF02736770]
Kosik, K. S., Orecchio, L. D., Bruns, G. A. P., Benowitz, L. I., MacDonald, G. P., Cox, D. R., Neve, R. L. Human GAP-43: its deduced amino acid sequence and chromosomal localization in mouse and human. Neuron 1: 127-132, 1988. [PubMed: 3272162] [Full Text: https://doi.org/10.1016/0896-6273(88)90196-1]
Reeves, R. H., O'Hara, B. F., Gearhart, J. D. Localization on mouse chromosome 16 of Smst and Gap43: a conserved synteny with human chromosome 3. (Abstract) Cytogenet. Cell Genet. 51: 1064, 1989.
Strittmatter, S. M., Fankhauser, C., Huang, P. L., Mashimo, H., Fishman, M. C. Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43. Cell 80: 445-452, 1995. [PubMed: 7859286] [Full Text: https://doi.org/10.1016/0092-8674(95)90495-6]