Disease relevance of GAP43

• In this study, we demonstrate that re-expression of GAP43 in deficient C6 glioma cells results in growth suppression in clonogenic assays, as well as in multiple independently derived C6 glioma cell lines in vitro [1].
• These data identify a novel set of compounds that modulate neurite outgrowth, and also support the notion that GAP-43 can alter neurite extension by modulating pertussis toxin-sensitive G-protein activity in the growth cone [2].
• We report here that the GAP-43 mRNA is also expressed transiently in developing limbs of chicken embryos, which contain axons of spinal cord and dorsal root ganglion neurons, but do not contain neuronal cell bodies [3].

Psychiatry related information on GAP43

• Passive avoidance learning induced change in GAP43 phosphorylation in day-old chicks [4].

High impact information on GAP43

• Retinal cultures transfected with a chDab1-L expression construct undergo a dramatic change in morphology, accompanied by the formation of numerous thin elongated processes, increased tyrosine phosphorylation, activation of Src family kinase(s) and increased levels of the axonal outgrowth protein growth-associated protein-43 [5].
• The 43-kD growth-associated protein (GAP-43) is a major protein kinase C (PKC) substrate of axonal growth cones, developing nerve terminals, regenerating axons, and adult central nervous system areas associated with plasticity [6].
• To identify aspects of GAP-43 function, we analyzed the actions of wild-type, membrane-association, and phosphorylation-site mutants of GAP-43 in nonneuronal cell lines [6].
• Phosphorylation-site mutagenesis of the growth-associated protein GAP-43 modulates its effects on cell spreading and morphology [6].
• The effects of GAP-43 on cell morphology required association with the cell membrane, since GAP-43(Ala3Ala4), a mutant that failed to associate with the cell cortex, had no morphogenetic activity [6].

Biological context of GAP43

• The predicted amino acid sequence for chicken GAP-43 displays extensive similarity to that of the mammalian protein, particularly in the amino-terminal region, to which functional domains of the protein have been assigned [7].
• Using multiplex gene expression profiling, we found that growth-associated protein 43 (GAP43) RNA and protein expression were lost in select human and mouse glioma cell lines [1].
• In addition, GAP43-expressing C6 clones demonstrate impaired cell motility and increased homophilic aggregation [1].
• However, administration of ACTH immediately posttraining led to both the formation of the long-term memory stage and a preceding significant increase in the phosphorylation of GAP43 [8].
• The GAP-43 constructs were introduced in L6 and COS-7 cells by transient transfection [6].

Anatomical context of GAP43

• In situ hybridization analysis reveals that GAP-43 RNA is expressed by several neural structures in the chick embryo, including derivatives of the neural tube, neural crest, and neuroectodermal placodes [7].
• The formation of a protein synthesis-dependent long-term memory stage in day-old chicks trained on a passive discriminated avoidance task has been shown to occur only with an adequate level of reinforcement, and is preceded by a significant change in the phosphorylation state of the forebrain synaptosomal membrane protein GAP43 protein [8].
• GAP43 identifies developing muscle cells in human embryos [9].
• GAP43 has long been regarded as a neurone specific molecule present intraneuronally in both the central and peripheral nervous system, especially during development and regeneration [9].
• Like the endogenous protein in neurons and their growth cones, GAP-43 in nonneuronal cells associated with the cell periphery [6].

Associations of GAP43 with chemical compounds

• GAP43-expressing C6 cells also exhibit reduced tumor growth as s.c. explants in immunocompromised mice in vivo [1].
• Cytosolic and depalmitoylated membrane-extracted GAP-43 were found to stimulate guanine nucleotide binding and exchange activity in chromaffin granule membranes [10].
• The chick protein and the rat GAP-43 are biochemically similar proteins that both serve as major targets of phosphorylation by endogenous protein kinase C. The detergent-resistant complex in which GAP-43 is found also contains actin (approximately 5% of the total protein) and a neurone-specific cell surface glycoprotein [11].
• In parallel with diC8-induced shape changes there is an accretion of f-actin and serine 41-phosphorylated GAP-43 in the entire axonal processes and the rounded growing tips [12].
• Role of highly conserved pyrimidine-rich sequences in the 3' untranslated region of the GAP-43 mRNA in mRNA stability and RNA-protein interactions [13].

Other interactions of GAP43

• The effect of imprinting, an early form of exposure learning, on the phosphorylation state of the protein kinase C substrates myristoylated alanine-rich C-kinase substrate (MARCKS) and protein F1/43-kDa growth-associated protein (F1/GAP-43) was studied in two regions of the chick forebrain [14].
• Assayed by immunoblots, this fraction is enriched in GAP-43, and contains the cytoskeletal proteins actin, myosin II, neurofilament protein, tubulin, kinesin, and dynamin [15].

Analytical, diagnostic and therapeutic context of GAP43

• Immunoblotting studies with monoclonal anti-GAP43 antibody indicate that this protein is GAP43 [4].
• In the prsent investigation, we have used immunohistochemistry to investigate whether GAP43 is also expressed in developing human muscle cell [9].
• Using this tissue culture system as well as neuronal cell culture we then studied the effects of diC8 on the shapes and actin-based motility of distal axonal processes and growth cones as well as on the spatial distribution of f-actin and serine 41-phosphorylated GAP-43 (neuromodulin, B50) [12].

References