Disease relevance of GAP43

• The subjects with end-stage kidney disease showed frank loss of both GAP43 immunoreactivity and olfactory glomeruli [1].
• Moreover, in vitro studies have demonstrated that the expression of B-50 in pheochromocytoma PC12 cells can be stimulated by the nerve growth factor (NGF) [2].
• Here, we studied the expression of NGF, LNGFR and B-50 in myopathy [2].
• Light microscopy study of low-affinity nerve growth factor receptor and phosphoprotein B-50/neuromodulin in inflammatory myopathies [2].
• Large ganglion cells showed upregulated neurofilament and GAP-43 expression, with neurites sprouting from somata and axon collaterals [3].

Psychiatry related information on GAP43

• (2) Learned helplessness increased the expression of GAP-43 two days and eight days after learned helplessness training [4].
• The temporal and spatial distribution of GAP-43 mRNA in early human development, from 6 to 23 gestational weeks (g.w.), was examined by in situ hybridization histochemistry [5].
• In contrast to patients with schizophrenia, GAP-43 and synaptophysin levels in subjects with bipolar disorder did not differ from controls [6].
• 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 [7].
• Aberrant GAP-43 gene expression in Alzheimer's disease [8].

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

• Furthermore, reexpression of one of these downregulated astrocytoma-associated proteins, GAP43, resulted in C6 glioma cell growth suppression [12].
• We found that GAP-43 was enriched in detergent-resistant membranes (DRMs) isolated by Triton X-100 extraction from PC12 pheochromocytoma cells and could be detected in detergent-insoluble plasma membrane remnants after extraction of cells in situ [13].
• The aim of this study was to compare immunoreactivities for substance P with other enteric neuropeptides and GAP-43, a general marker for enteric nerves, in normal human colon and in different stages of ulcerative colitis [14].
• Whereas all neuroblastomas express growth-associated protein-43, neuropeptide tyrosine, and Bcl-2, tumors with differentiating cells with neuroendocrine features expressed these genes only in the morphologically immature, proliferating cells [15].
• By using this technique, endogenous gamma-aminobutyric acid and glutamic acid decarboxylase activity were detected in two rat neuroblastomas, B35 and B50, a human medulloblastoma cell line, TE671, and cultured human skin fibroblasts [16].

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

• The neuronal growth-associated protein GAP-43 interacts with rabaptin-5 and participates in endocytosis [19].
• The C-terminal part of caldesmon contains three peptides with a primary structure similar to that of the calmodulin- and phospholipid-binding site of neuromodulin [26].

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

• In the axotomized retinas, ciliary neurotrophic factor initiated sprouting of axon-like processes at 14 and 28 days post-axotomy and up-regulated the expression level of growth-associated protein-43 messenger RNA at 7, 14 and 28 days post-axotomy [28].
• This suggests that neuronal GAP-43 may serve as an intracellular signal to greatly enhance the sensitivity of G protein-coupled receptor transduction [29].
• The neuronal cytosolic protein GAP-43 stimulates G alpha o in purified chromaffin granule membranes and inhibits exocytosis in permeabilized cells [30].
• In the ST, GAP-43 differed significantly among hypoxic and control animals and the two-way ANOVA revealed significant differences with age (F = 3.23; P = 0.037) and treatment (F = 4.84; P = 0.036) [31].

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

• These staining patterns formed the basis of a retinal pathology scoring system, and immunohistochemistry was also used to detect CD68, neurofilaments, protein kinase C, growth-associated protein-43, and a pan-cone-specific enzymatic marker [3].
• Using in situ hybridization, we have investigated growth-associated protein-43 mRNA in the medial temporal lobe and cerebral cortex in 11 normal subjects and 11 matched subjects with schizophrenia, a disorder in which perturbed neurodevelopment and aberrant plasticity are implicated [20].
• The Mabs are produced against the bovine B-50, selected by ELISA for cross-reactivity with its human counterpart, and evaluated on Western blots in comparison with the well-characterized affinity-purified rabbit polyclonal antibodies to rat-B-50 [21].
• Double immunofluorescence staining was performed on dissociated cell cultures using antibodies to glial fibrillary acidic protein (GFAP) and to GAP-43 [36].
• Total cellular RNA was extracted from cell pellets and reverse transcribed into cDNA; cDNA was subjected to PCR amplification using primers specific for GAP-43 and PCR products were separated through polyacrylamide gels [36].

References