gap 43 protein


Summary: A nervous tissue specific protein which is highly expressed in NEURONS during development and NERVE REGENERATION. It has been implicated in neurite outgrowth, long-term potentiation, SIGNAL TRANSDUCTION, and NEUROTRANSMITTER release. (From Neurotoxicology 1994;15(1):41-7) It is also a substrate of PROTEIN KINASE C.

Top Publications

  1. Gauthier Campbell C, Bredt D, Murphy T, El Husseini A. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004;15:2205-17 pubmed
    ..These results demonstrate that select dually lipidated protein motifs trigger changes in the development and growth of neuronal processes. ..
  2. Liu S, Tian Y, Chlenski A, Yang Q, Zage P, Salwen H, et al. Cross-talk between Schwann cells and neuroblasts influences the biology of neuroblastoma xenografts. Am J Pathol. 2005;166:891-900 pubmed
    ..Our results indicate that infiltrating Schwann cells of mouse origin are capable of promoting human neuroblast differentiation, inducing apoptosis, and inhibiting proliferation and angiogenesis in vivo. ..
  3. Cafferty W, Gardiner N, Das P, Qiu J, McMahon S, Thompson S. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice. J Neurosci. 2004;24:4432-43 pubmed
    ..We suggest that injury-induced IL-6 upregulation is required to promote regeneration within the CNS. Our results indicate that this is achieved through a boosted growth state of dorsal column projecting sensory neurons. ..
  4. Qiu J, Cafferty W, McMahon S, Thompson S. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci. 2005;25:1645-53 pubmed
    ..We conclude that STAT3 activation is necessary for increased growth ability of DRG neurons and improved axonal regeneration in the spinal cord after a conditioning injury. ..
  5. Gupta S, Mishra R, Kusum S, Spedding M, Meiri K, Gressens P, et al. GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986. Cell Death Differ. 2009;16:624-37 pubmed publisher
  6. Shen Y, Mani S, Donovan S, Schwob J, Meiri K. Growth-associated protein-43 is required for commissural axon guidance in the developing vertebrate nervous system. J Neurosci. 2002;22:239-47 pubmed
    ..Nonetheless, the data show that a functional threshold of GAP-43 is required for commissure formation and suggests that failure to regulate F-actin in commissural growth cones may be related to inhibited PKC phosphorylation of GAP-43. ..
  7. Kwon B, Liu J, Messerer C, Kobayashi N, McGraw J, Oschipok L, et al. Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A. 2002;99:3246-51 pubmed
    ..This outcome is a demonstration of the regenerative capacity of spinal cord projection neurons a full year after axotomy. ..
  8. Donovan S, Mamounas L, Andrews A, Blue M, McCasland J. GAP-43 is critical for normal development of the serotonergic innervation in forebrain. J Neurosci. 2002;22:3543-52 pubmed
    ..These results suggest that GAP-43 is a key regulator in normal pathfinding and arborization of 5-HT axons during early brain development. ..
  9. Siconolfi L, Seeds N. Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. J Neurosci. 2001;21:4348-55 pubmed
    ..These studies clearly showed that PAs were necessary for timely functional recovery by regenerating peripheral nerves. ..

More Information


  1. Ikegami T, Nakamura M, Yamane J, Katoh H, Okada S, Iwanami A, et al. Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury. Eur J Neurosci. 2005;22:3036-46 pubmed
  2. MacDermid V, McPhail L, Tsang B, Rosenthal A, Davies A, Ramer M. A soluble Nogo receptor differentially affects plasticity of spinally projecting axons. Eur J Neurosci. 2004;20:2567-79 pubmed
    ..These results reveal a differential effect of myelin antagonism on distinct populations of spinally projecting axons. ..
  3. Chao T, Pham K, Steward O, Gupta R. Chronic nerve compression injury induces a phenotypic switch of neurons within the dorsal root ganglia. J Comp Neurol. 2008;506:180-93 pubmed
    ..Thus, CNC induces a phenotypic change in the DRG that appears to be temporally associated with increases in GDNF protein expression at and near the site of the compression injury in the nerve...
  4. Burgess A, Weng Y, Ypsilanti A, Cui X, Caines G, Aubert I. Polysialic acid limits septal neurite outgrowth on laminin. Brain Res. 2007;1144:52-8 pubmed
    ..Taken together, these results indicate that the removal of PSA from septal neurons increases neurite outgrowth on laminin by promoting interactions between beta1-integrin and laminin. ..
  5. Song X, Li F, Zhang F, Zhong J, Zhou X. Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury. PLoS ONE. 2008;3:e1707 pubmed publisher
  6. El Meskini R, Crabtree K, Cline L, Mains R, Eipper B, Ronnett G. ATP7A (Menkes protein) functions in axonal targeting and synaptogenesis. Mol Cell Neurosci. 2007;34:409-21 pubmed
    ..This study demonstrates a role for ATP7A and/or copper in axon outgrowth and synaptogenesis, and will further help identify the cause of the neuropathology that characterizes MD. ..
  7. Klebanov O, Nitzan A, Raz D, Barzilai A, Solomon A. Upregulation of Semaphorin 3A and the associated biochemical and cellular events in a rat model of retinal detachment. Graefes Arch Clin Exp Ophthalmol. 2009;247:73-86 pubmed publisher
    ..In addition, further study is required on several other factors that may affect visual acuity, such as size and location of the detached area and the time lapse between detachment and surgery. ..
  8. Kajimura D, Dragomir C, Ramirez F, Laub F. Identification of genes regulated by transcription factor KLF7 in differentiating olfactory sensory neurons. Gene. 2007;388:34-42 pubmed
    ..Collectively, these results advance knowledge of transcriptional regulation of olfactory neurogenesis and KLF7 action. ..
  9. Huang W, Kuo W, Cherng J, Hsu S, Chen P, Huang S, et al. Chondroitinase ABC promotes axonal re-growth and behavior recovery in spinal cord injury. Biochem Biophys Res Commun. 2006;349:963-8 pubmed
  10. Lu J, Zheng Y, Luo L, Wu D, Sun D, Feng Y. Quercetin reverses D-galactose induced neurotoxicity in mouse brain. Behav Brain Res. 2006;171:251-60 pubmed
    ..We found that quercetin dramatically elevated the GAP43 mRNA expression in the brain of D-gal-treated mice to regenerate normal function of neurons against the cellular injury caused by D-gal. ..
  11. Harris W, Sachana M, Flaskos J, Hargreaves A. Neuroprotection from diazinon-induced toxicity in differentiating murine N2a neuroblastoma cells. Neurotoxicology. 2009;30:958-64 pubmed publisher
    ..In conclusion, these data demonstrate that C6 conditioned medium protects N2a cells from the neurite inhibitory effects of diazinon by blocking molecular events leading to axon damage and that GDNF is implicated in these effects. ..
  12. Bacsi A, Stanton G, Hughes T, Kruze M, Boldogh I. Colostrinin-driven neurite outgrowth requires p53 activation in PC12 cells. Cell Mol Neurobiol. 2005;25:1123-39 pubmed
    ..4. We conclude that CLN induces delicate cassettes of signaling pathways common to cell proliferation and differentiation, and mediates activities that are similar to those of hormones and neurotrophins, leading to neurite outgrowth. ..
  13. Kelly E, Tremblay M, McCasland J, Majewska A. Postsynaptic deregulation in GAP-43 heterozygous mouse barrel cortex. Cereb Cortex. 2010;20:1696-707 pubmed publisher
    ..Taken together, our findings suggest abnormal postsynaptic differentiation in GAP-43 HZ cortex during early barrel development, followed by adaptive compensation and partial phenotypic rescue. ..
  14. Neuhuber B, Timothy Himes B, Shumsky J, Gallo G, Fischer I. Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res. 2005;1035:73-85 pubmed
    ..To qualify MSC lots for future clinical application, such notable differences in donor or lot-lot efficacy highlight the need for establishing adequate characterization, including the development of relevant efficacy assays. ..
  15. Ma J, Shen J, Lee C, Elsaidi G, Smith T, Walker F, et al. Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: a study in rats. J Orthop Res. 2005;23:302-9 pubmed
    ..Although GAP-43 participates in nerve sprouting, no increase of GAP-43 mRNA occurred following BoNT-A. Delayed up-regulation of SNAP-25 mRNA might be associated with muscle functional recovery. ..
  16. Korteweg N, Maia A, Verhage M, Burbach J. Development of the mouse hypothalamo-neurohypophysial system in the munc18-1 null mutant that lacks regulated secretion. Eur J Neurosci. 2004;19:2944-52 pubmed
    ..Thus, the communication between the outgrowing neurons and the pituicytes could serve to integrate these two cell types to constitute a functional peptidergic system. ..
  17. Zhao C, Zhang C, Wang Y, Zhou S, Zhou C, Li W, et al. Signals in pathological CNS extracts of ALS mice promote hMSCs neurogenic differentiation in vitro. Cell Biol Int. 2007;31:1428-35 pubmed
    ..These results show that pathological condition of ALS is endowed with capacity to induce hMSCs neurogenic differentiation and hMSCs have shown a potential candidate in cellular therapy for ALS. ..
  18. Oliveira D, Sanada P, Saragossa Filho A, Innocenti L, Oler G, Cerutti J, et al. Neuromodulatory property of standardized extract Ginkgo biloba L. (EGb 761) on memory: behavioral and molecular evidence. Brain Res. 2009;1269:68-89 pubmed publisher
    ..All together, our findings not only provide new evidence for a role of EGb 761 on memory but also identify molecular changes that underlie the fear memory consolidation. ..
  19. Miranda Saksena M, Boadle R, Aggarwal A, Tijono B, Rixon F, Diefenbach R, et al. Herpes simplex virus utilizes the large secretory vesicle pathway for anterograde transport of tegument and envelope proteins and for viral exocytosis from growth cones of human fetal axons. J Virol. 2009;83:3187-99 pubmed publisher
    ..We postulate that HSV-1 capsids invaginate tegument- and envelope-bearing TGN-derived vesicles and utilize the large secretory vesicle pathway of exocytosis for exit from axons. ..
  20. Di Toro R, Baiula M, Spampinato S. Expression of the repressor element-1 silencing transcription factor (REST) is influenced by insulin-like growth factor-I in differentiating human neuroblastoma cells. Eur J Neurosci. 2005;21:46-58 pubmed
    ..These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance. ..
  21. Ahmed Z, Read M, Berry M, Logan A. Satellite glia not DRG neurons constitutively activate EGFR but EGFR inactivation is not correlated with axon regeneration. Neurobiol Dis. 2010;39:292-300 pubmed publisher
    ..Together, these data argue against a direct intra-axonal involvement of pEGFR in axon regeneration. ..
  22. Penas C, Casas C, Robert I, Forés J, Navarro X. Cytoskeletal and activity-related changes in spinal motoneurons after root avulsion. J Neurotrauma. 2009;26:763-79 pubmed publisher
    ..This study presents a detailed description of motoneuron reaction after root avulsion, which suggests an early time-window during the first 2 weeks for attempts to repair the injury and promote motoneuron survival and regeneration...
  23. von Schantz C, Saharinen J, Kopra O, Cooper J, Gentile M, Hovatta I, et al. Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases. BMC Genomics. 2008;9:146 pubmed publisher
    ..Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCLs as well. ..
  24. Pascale A, Amadio M, Scapagnini G, Lanni C, Racchi M, Provenzani A, et al. Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway. Proc Natl Acad Sci U S A. 2005;102:12065-70 pubmed
    ..These findings suggest a model for gene expression regulation by nELAV proteins through a PKCalpha-dependent pathway that is relevant for the cellular programs in which ARE-mediated control plays a pivotal role. ..
  25. Dawley E, Nelsen M, Lopata A, Schwartz J, Bierly A. Cell birth and survival following seasonal periods of cell proliferation in the chemosensory epithelia of red-backed salamanders, Plethodon cinereus. Brain Behav Evol. 2006;68:26-36 pubmed
    ..We suggest that vomeronasal receptor neurons born in late spring function throughout the summer and may be associated with the animals' extensive territoriality during that period. ..
  26. Afadlal S, Polaboon N, Surakul P, Govitrapong P, Jutapakdeegul N. Prenatal stress alters presynaptic marker proteins in the hippocampus of rat pups. Neurosci Lett. 2010;470:24-7 pubmed publisher
    ..These changes may be associated with stress-induced impairment of hippocampal function that occurs in later life of the offspring. ..
  27. Carulli D, Buffo A, Strata P. Reparative mechanisms in the cerebellar cortex. Prog Neurobiol. 2004;72:373-98 pubmed
    ..In contrast, in Purkinje cells, poor intrinsic regenerative capabilities and myelin-derived signals stabilise the mature connectivity and prevent axonal regeneration after lesion. ..
  28. Viberg H, Pontén E, Eriksson P, Gordh T, Fredriksson A. Neonatal ketamine exposure results in changes in biochemical substrates of neuronal growth and synaptogenesis, and alters adult behavior irreversibly. Toxicology. 2008;249:153-9 pubmed publisher
  29. Kuroki M, Sawasaki Y, Kuroki K, Takeuchi K, Yoshioka M. Culture of porcine fetal pancreatic neurons. Pancreas. 2008;37:203-9 pubmed publisher
    ..Using our method, neuronal cells were readily cultured from pancreatic tissue. These cells will be useful in elucidating the physiology and pharmacology of pancreatic neurons. ..
  30. Ranasinghe H, Williams C, Christophidis L, Mitchell M, Fraser M, Scheepens A. Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury. Neuroscience. 2009;158:732-44 pubmed publisher
    ..Conversely, MMP-9 appeared to be associated with more acute processes during the period of lesion development. ..
  31. Nathan B, Nisar R, Short J, Randall S, Grissom E, Griffin G, et al. Delayed olfactory nerve regeneration in ApoE-deficient mice. Brain Res. 2005;1041:87-94 pubmed
    ..Together, these results show that olfactory nerve regeneration is significantly slower in KO mice as compared to WT mice, suggesting apoE facilitates olfactory nerve regeneration. ..
  32. Jiang H, Lu Z, Yu Y, Zhao D, Jian X, Yang B, et al. Effects of metoprolol on sympathetic remodeling and electrical remodeling at infarcted border zone after myocardial infarction in rabbits. Cardiology. 2007;108:176-82 pubmed
    ..Metoprolol can inhibit sympathetic remodeling and electrical remodeling at the IBZ after MI. The association of metoprolol with improved electrical remodeling may be partly related to the inhibition of sympathetic remodeling. ..
  33. Shyu W, Li K, Peng H, Lin S, Liu R, Wang H, et al. Induction of GAP-43 modulates neuroplasticity in PBSC (CD34+) implanted-Parkinson's model. J Neurosci Res. 2009;87:2020-33 pubmed publisher
    ..In addition, a significant increase in neurotrophic factor expression was found in the ipsilateral hemisphere of the PBSC-treated group. In summary, this protocol may be a useful strategy for the treatment of clinical PD. ..
  34. Thauerer B, zur Nedden S, Baier Bitterlich G. Vital role of protein kinase C-related kinase in the formation and stability of neurites during hypoxia. J Neurochem. 2010;113:432-46 pubmed publisher
    ..Based on these data, a putative role of PRK1 as a key-signaling element for the successive NGF- and purine nucleoside-mediated protection of hypoxic neuronal cells is hypothesized. ..
  35. Kraus K, Ding D, Zhou Y, Salvi R. Central auditory plasticity after carboplatin-induced unilateral inner ear damage in the chinchilla: up-regulation of GAP-43 in the ventral cochlear nucleus. Hear Res. 2009;255:33-43 pubmed publisher
    ..Alternatively, massive fiber growth may represent a deleterious process causing central hyperactivity that leads to loudness recruitment or tinnitus. ..
  36. Chen L, Wang Y, Li G, Li H. [The effects of an NGF isolated and purified from venom of Naja naja atra on GAP-43 in spinal cord dorsal horn of cats subjected to partial rhizotomy]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005;36:622-4 pubmed
  37. López Jiménez M, Bartolomé Martín D, Sanchez Prieto J, Torres M. Suppression of guanylyl cyclase (beta1 subunit) expression impairs neurite outgrowth and synapse maturation in cultured cerebellar granule cells. Cell Death Differ. 2009;16:1266-78 pubmed publisher
    ..These findings highlight the importance of sGC in the regulation of neurite outgrowth and synapse formation, and in the functional maturation of cerebellar granule cells in vitro. ..
  38. Nathan B, Gairhe S, Nwosu I, Clark S, Struble R. Reconstitution of the olfactory epithelium following injury in apoE-deficient mice. Exp Neurol. 2010;226:40-6 pubmed publisher
    ..The data suggest that apoE production increases in the injured OE to facilitate maturation of olfactory sensory neurons. ..
  39. Hanaya R, Boehm N, Nehlig A. Dissociation of the immunoreactivity of synaptophysin and GAP-43 during the acute and latent phases of the lithium-pilocarpine model in the immature and adult rat. Exp Neurol. 2007;204:720-32 pubmed
    ..Synaptophysin appears to be a more sensitive marker of plasticity induced by SE than GAP-43. ..
  40. Yamada M, Terayama R, Bando Y, Kasai S, Yoshida S. Regeneration of the abdominal postganglionic sympathetic system. Neurosci Res. 2006;54:261-8 pubmed
    ..Therefore, postganglionic sympathetic nerves in the abdomen are able to regenerate and reinnervation occurs even after the removal of sympathetic ganglia. ..
  41. Zhang Y, Bo X, Schoepfer R, Holtmaat A, Verhaagen J, Emson P, et al. Growth-associated protein GAP-43 and L1 act synergistically to promote regenerative growth of Purkinje cell axons in vivo. Proc Natl Acad Sci U S A. 2005;102:14883-8 pubmed
  42. Charbaut E, Chauvin S, Enslen H, Zamaroczy S, Sobel A. Two separate motifs cooperate to target stathmin-related proteins to the Golgi complex. J Cell Sci. 2005;118:2313-23 pubmed
    ..More generally we provide new information on essential mechanisms of functional protein subcellular targeting. ..
  43. Das K, Freudenrich T, Mundy W. Assessment of PC12 cell differentiation and neurite growth: a comparison of morphological and neurochemical measures. Neurotoxicol Teratol. 2004;26:397-406 pubmed
    ..However, ET-18 did not alter the expression of GAP-43 or synapsin I. These data suggest that GAP-43 may be a useful indicator of the status of PC12 cell differentiation. ..
  44. Zhao H, Wang Y, Yin Z. A comparison of LEDGFp52 and CNTF on the in vitro growth of rat retinal ganglion cell neurites. Neurosci Lett. 2008;440:9-13 pubmed publisher
    ..The positive action of the LEDGFp52 protein was similar to or more efficacious than CNTF. LEDGFp52 appears to be an important regulatory protein for the growth of cell processes. ..
  45. Lieu A, Li J, Webb D, Hankins G, Howng S, Helm G. Functions of G protein-coupled receptor kinase interacting protein 1 in human neuronal (NT2N) cells. J Neurosurg. 2006;105:103-10 pubmed
    ..The GIT1-beta-PIX-Cdc42-PAK pathway may play an important role in neuronal outgrowth. ..
  46. Gupta R, Rummler L, Palispis W, Truong L, Chao T, Rowshan K, et al. Local down-regulation of myelin-associated glycoprotein permits axonal sprouting with chronic nerve compression injury. Exp Neurol. 2006;200:418-29 pubmed
    ..These data demonstrate that CNC injury triggers axonal sprouting and suggests that a local down-regulation of MAG within the peripheral nerve secondary to CNC injury is the critical signal for the sprouting response. ..
  47. Mielke J, Comas T, Woulfe J, Monette R, Chakravarthy B, Mealing G. Cytoskeletal, synaptic, and nuclear protein changes associated with rat interface organotypic hippocampal slice culture development. Brain Res Dev Brain Res. 2005;160:275-86 pubmed
  48. Shiohira H, Kitaoka A, Shirasawa H, Enjoji M, Nakashima M. Am80 induces neuronal differentiation in a human neuroblastoma NH-12 cell line. Int J Mol Med. 2010;26:393-9 pubmed
    ..These findings suggest that Am80 induces neuronal differentiation to a greater extent than ATRA and thus may help establishing therapeutic strategies against neuronal degenerative disorders such as Parkinson's disease. ..
  49. Yang H, Xia Y, Lu S, Soong T, Feng Z. Basic fibroblast growth factor-induced neuronal differentiation of mouse bone marrow stromal cells requires FGFR-1, MAPK/ERK, and transcription factor AP-1. J Biol Chem. 2008;283:5287-95 pubmed publisher
  50. Davis E, Coyne C, McNeill T. Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion. Neuroscience. 2007;146:784-91 pubmed
  51. Zou W, Wang H, Liu J, Zhang H, An L. [Expression of caveolin-1 protein in the rat brain and its role in the discrimination learning]. Sheng Li Xue Bao. 2006;58:429-34 pubmed
    ..These results suggest that Cav-1 protein is involved in BDL and plays an important role in the plasticity of central nervous system. ..
  52. Paz R, Andreasen N, Daoud S, Conley R, Roberts R, Bustillo J, et al. Increased expression of activity-dependent genes in cerebellar glutamatergic neurons of patients with schizophrenia. Am J Psychiatry. 2006;163:1829-31 pubmed
    ..These results suggest that glutamatergic neurons may be hyperactive in the cerebellar cortices of patients with schizophrenia. ..
  53. Arteaga M, Gutierrez R, Avila J, Mobasheri A, Diaz Flores L, Martin Vasallo P. Regeneration influences expression of the Na+, K+-atpase subunit isoforms in the rat peripheral nervous system. Neuroscience. 2004;129:691-702 pubmed
    ..This adaptation may be important for regeneration. ..