Disease relevance of Gap43

• Using in situ hybridization, the mean percentage of GAP-43 mRNA-labeled neurons (signal : noise ratio > or = 10) was observed to have increased significantly to approximately 60% for 1-7 days after CT injury, while that in the naive ganglion was < 15% [1].
• Increase in GAP-43 mRNA, suggesting CT axonal regeneration, may have a role in recovery from taste disorders [1].
• Neuronal damage and plasticity identified by microtubule-associated protein 2, growth-associated protein 43, and cyclin D1 immunoreactivity after focal cerebral ischemia in rats [2].
• Growth-associated protein 43 (GAP-43), which is a marker of growth cone formation, was observed at the site of coaptation in the LGN 7 days postoperatively and in the MGN at the site of coaptation at 14 days [3].
• In order to reveal axonal rewiring in the hippocampal and parahippocampal regions after status epilepticus, we investigated the temporal evolution of growth-associated protein-43 (GAP-43) mRNA and protein expression in two rat models of mesial temporal lobe epilepsy (MTLE) [4].

Psychiatry related information on Gap43

• These results further strengthen the involvement of NAc and VTA in the behavioural sensitization and suggest a role of GAP-43 in the synaptic reorganization associated to drug abuse [5].

High impact information on Gap43

• Targeting of neuromodulin (GAP-43) fusion proteins to growth cones in cultured rat embryonic neurons [6].
• Zuber and co-workers have proposed that the N-terminal 10 amino acid sequence of neuromodulin is sufficient to target proteins to growth cones [6].
• Neuromodulin (also called GAP43, G50, F1, pp46), a neural-specific calmodulin binding protein, is a major protein kinase C substrate found in developing and regenerating neurons [7].
• Thus, all three macroglial cell types of the central nervous system (type I and type 2 astrocytes and oligodendrocytes) contain GAP-43 [8].
• Although neuromodulin in oligodendrocytes is soluble in 2.5% perchloric acid like the neuronal counterpart it migrates essentially as a single protein spot on two-dimensional gel electrophoresis whereas the neuronal antigen can be resolved into at least three distinct protein spots [7].

Chemical compound and disease context of Gap43

• In order to further characterize synaptic alterations following a severe lesion of the nigrostriatal system, the expression of synaptic marker proteins, synaptophysin and growth-associated protein-43 (GAP-43), was examined in various brain regions of 6-hydroxydopamine (6-OHDA)-treated rats, an animal model of Parkinson's disease [9].
• The density and distribution of reactivity for two lectins (soybean agglutinin (SBA) and RL-29), growth associated protein-43 (GAP-43) and the neuropeptides substance P and calcitonin gene-related peptide were analyzed in the spinal cord dorsal horn of rats with an experimental peripheral neuropathy [10].
• The expression of GAP43 mRNA in noradrenaline-producing chromaffin cells and type I ganglion neurons suggests an important role for GAP43 in these cells both during development and in adult life [11].
• Glutamate N-methyl-D-aspartate receptor blockade prevents induction of GAP-43 after focal ischemia in rats [12].
• High levels of GAP43 mRNA were found in intra-adrenal ganglion neurons also expressing neuropeptide tyrosine (NPY) mRNA (type I ganglion neurons), and at prenatal and early postnatal stages in large medullarly clusters of NPY mRNA containing cells, probably representing type I ganglion neurons precursors [11].

Biological context of Gap43

• Here we report that overexpression of HuD protein in PC12 cells stabilizes the GAP-43 mRNA by delaying the onset of mRNA degradation and that this process depends on the size of the poly(A) tail [13].
• In the present study we measured the expression of select proteins associated with neurite damage and plasticity (MAP-2 and GAP-43) as well as cell cycle (cyclin D1) after induction of focal cerebral ischemia in the rat [2].
• Repetitive daily exposure to static magnetic fields at 100 mT for 15 min led to a decrease in the expression of MAP-2, without significantly affecting cell viability or the expression of neuronal nuclei (NeuN) and GAP-43 [14].
• Protein F1 is a neuron-specific, synaptic-enriched, membrane-bound substrate of protein kinase C (PKC) whose phosphorylation is related to synaptic plasticity in the adult [15].
• Genetic or pharmacological inactivation of PKCalpha abolishes nELAV protein cytoskeletal up-regulation, GAP-43 mRNA stabilization, and GAP-43 protein increase, demonstrating the primary role of this specific PKC isozyme in the cascade of nELAV recruitment [16].

Anatomical context of Gap43

• Developmental profiles of growth-associated protein (Gap43), Ngfb, Bndf and Ntf4 mRNA levels in the rat forebrain after exposure to 60 Hz magnetic fields [17].
• Expression of activating transcription factor 3 and growth-associated protein 43 in the rat geniculate ganglion neurons after chorda tympani injury [1].
• METHODS: Brains from rats (n=28) subjected to 2 hours of middle cerebral artery occlusion and 6 hours, 12 hours, and 2, 7, 14, 21, and 28 days (n=4 per time point) of reperfusion and control sham-operated (n=3) and normal (n=2) rats were processed by immunohistochemistry with antibodies raised against MAP-2, GAP-43, and cyclin D1 [2].
• CONCLUSIONS: The selective expressions of the neuronal structural proteins (MAP-2 in dendrites and GAP-43 in axons) and the cyclin D1 cell cycle protein in neurons observed in the boundary zone to the ischemic core are suggestive of compensatory and repair mechanisms in ischemia-damaged neurons after transient focal cerebral ischemia [2].
• Effect of chronic restraint stress and tianeptine on growth factors, growth-associated protein-43 and microtubule-associated protein 2 mRNA expression in the rat hippocampus [18].

Associations of Gap43 with chemical compounds

• Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-binding protein HuD [13].
• The increase in T alpha 1, MAP-2 and GAP-43 mRNA levels following glutamate exposure was mediated via both N-methyl-D-aspartate and metabotropic receptor activation [19].
• These were determined to be axons based on: (i) morphological criteria including size and presence of growth cones, (ii) synaptophysin and growth-associated protein-43 immunoreactivity, (iii) lack of glial fibrillary acidic protein immunoreactivity and (iv) contiguity of biocytin-filled processes with neuronal soma within the explant [20].
• Quantitative immunohistochemistry revealed a dose-dependent downregulation of spinophilin, a spine marker, and of synaptophysin, a presynaptic marker, and of growth-associated protein 43 after letrozole treatment [21].
• The CaM-mediated inhibition of Nm or Ng phosphorylation by PKM was also not affected by PS/DG either with or without Ca2+ [22].

Physical interactions of Gap43

• We conclude that HuD stabilizes the GAP-43 mRNA through a mechanism that is dependent on the length of the poly(A) tail and involves changes in its affinity for the mRNA [13].
• The time course for accumulation of FKBP-12 in sciatic nerve segments following nerve crush indicates rapid axonal transport at a rate similar to GAP-43 [23].

Enzymatic interactions of Gap43

• Calmodulin and de-phosphorylated B-50/growth-associated protein-43 (GAP-43) have been shown to bind in vitro in a molecular complex, but evidence for an in situ association in the nervous system does not exist [24].
• We reported previously that phosphorylated neuromodulin and phosphorylated synapsin I content increased in the striata of amphetamine-sensitized rats; however, the neuronal pathways responsible for the increase were unclear [25].

Co-localisations of Gap43

• Over 60% of the plasma membrane-associated calmodulin co-localized with B-50/GAP-43 in a non-random distribution [24].
• In control rats, fibres travelling in a stereotyped ladder-like pattern in the thoracic gray matter contained growth-associated protein-43 co-localized with dopamine beta-hydroxylase or substance P [26].
• E-FABP colocalized with GAP-43 at E14 through P10 [27].

Regulatory relationships of Gap43

• Sustained perineural infusion of the Janus kinase 2 (JAK2) inhibitor AG490 to the proximal nerve stump can block STAT3 phosphorylation after sciatic nerve transection and results in reduced growth-associated protein 43 upregulation and compromised neurite outgrowth in vitro [28].
• Calmodulin at 3.6 microM inhibited 95% of protein F1 phosphorylation by PKC [29].
• TGF-beta s and cAMP regulate GAP-43 expression in Schwann cells and reveal the association of this protein with the trans-Golgi network [30].
• Intracisternal antisense oligonucleotide to growth associated protein-43 blocks the recovery-promoting effects of basic fibroblast growth factor after focal stroke [31].

Other interactions of Gap43

• This stabilization was specific for GAP-43 mRNA containing the HuD binding element in the 3'-untranslated region and a poly(A) tail of at least 150 A nucleotides [13].
• S100 was ineffective in inhibiting the phosphorylation of Nm and Ng without Ca2+ and only poorly effective in the presence of Ca2+ [22].
• This administration of neurotrophic factor to the cell body resulted in increased expression of growth-associated protein-43 and Talpha1 tubulin, genes thought to be related to axonal regeneration [32].
• Infection down-regulated the expression of synaptophysin and growth-associated protein-43, two molecules involved in neuronal plasticity, as well as the expression of the chromaffin-specific gene tyrosine hydroxylase [33].
• Nestin-IR neurons had a mean diameter of 20.78 +/- 2.5 microm and expressed the neuronal markers neurofilament 200, betaIII-tubulin, protein gene product 9.5, growth associated protein 43, trkA, and calcitonin gene-related peptide [34].

Analytical, diagnostic and therapeutic context of Gap43

• However, we did not find significant alteration of protein expression levels for synaptophysin, GAP-43, and BDNF by using Western blot analysis [35].
• The peak period of GAP-43 expression in the NA is different from those in the facial and hypoglossal nuclei after axotomy [36].
• In a control group, immunoreactivity for GAP-43 was positive in the developing annulospiral endings of 2-week-old rats, but was not detected in any of the muscle spindles after 3 weeks of age [37].
• The effects of complete loss of occlusion on the structural and functional status of these muscle spindles were investigated by immunohistochemistry either for protein gene product 9.5 (PGP 9.5) or growth-associated protein-43 (GAP-43) by light and electron microscopy [37].
• To obtain precise alignments of the different neuromodulin spots from these two cell types, oligodendrocyte and neuronal cell extracts were mixed together and run on the same two-dimensional gel electrophoresis system [7].

References