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Query: UNIPROT:P06889 (Mol)
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The neuronal phosphoprotein B-50/GAP-43 has been implicated in neuritogenesis during developmental stages of the nervous system and in regenerative processes and neuronal plasticity in the adult. The protein appears to be a member of a family of acidic substrates of protein kinase C (PKC) that bind calmodulin at low calcium concentrations. Two of these substrates, B-50 and neurogranin, share the primary sequence coding for the phospho- and calmodulin-binding sites and might exert similar functions in axonal and dendritic processes, respectively. In the adult brain, B-50 is exclusively located at the presynaptic membrane. During neuritogenesis in cell culture, the protein is translocated to the growth cones, i.e., into the filopodia. In view of many positive correlations between B-50 expression and neurite outgrowth and the specific localization of B-50, a role in growth cone function has been proposed. Its phosphorylation state may regulate the local intracellular free calmodulin and calcium concentrations or vice versa. Both views link the B-50 protein to processes of signal transduction and transmitter release.
Mol Neurobiol 1991
PMID:Role of the growth-associated protein B-50/GAP-43 in neuronal plasticity. 184 Apr 22

We found that the level of nerve growth factor receptor (NGF-R) mRNA in facial motoneurons was increased after both facial nerve crushing and transection by means of in situ hybridization histochemistry. The increased level of NGF-R mRNA was maintained for at least 8 weeks after facial nerve transection, while facial nerve crushing caused only a transient increase. Thus, expression of NGF-R mRNA paralleled the axonal regeneration process. In addition, the increase of NGF-R mRNA with crushing was more pronounced than with transection from the 3rd to the 14th day after the insult.
Brain Res Mol Brain Res 1991 Jan
PMID:Effects of nerve crush and transection on mRNA levels for nerve growth factor receptor in the rat facial motoneurons. 185 72

In strain 129/Sv-ter mice, teratomas develop spontaneously during the 13th day of gestation. These testicular germ cell tumors exhibit characteristics of different germ layers closely resembling normal embryonic tissue. We investigated the interrelationship between nervous and muscular tissues (often found side by side) in teratomas of 4-week-old 129/Sv-ter mice. In well-differentiated mouse teratomas, histochemically and immunohistochemically distinct muscle fiber types could be distinguished, but not with all reactions. According to its aerobic oxidative capacity, teratoma muscle tissue was comparable with normal muscles. However, with respect to myosin-related properties, fiber type differentiation was incomplete. The muscle fibers - generally arranged in bundles - contained one centrally located endplate which was contacted mostly by a single nerve terminal. From this, proper endplate zones within the fiber bundles were formed. Occasionally "type grouping" was encountered, suggesting collateral axonal branching paralleled by synapse elimination. Together with the earlier in vivo observation of muscular contractions, we assume that teratoma muscle fibers are innervated by nerve cells (within the nervous tissue compartments) corresponding to spinal motoneurons. Thus, myogenesis, maturation and innervation of skeletal muscular tissue in mouse teratomas are largely comparable to normal development.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Innervation and maturation of muscular tissue in testicular teratomas in strain 129/Sv-ter mice. 198 Jan 72

The neuronal growth associated protein GAP-43 is expressed at high levels during axonal growth and regeneration. In this report, we describe the transfection of the nerve growth factor (NGF)-responsive pheochromocytoma cell line PC12 with the human GAP-43 cDNA under the control of the Moloney murine leukemia virus long terminal repeat (MoMuLV LTR). Two PC12 subclones were isolated that constitutively expressed GAP-43 from the transfected cDNA and showed increased responsiveness to NGF. Of the two transfected PC12 subclones, the subclone expressing the most human GAP-43 RNA showed an accelerated initial neurite outgrowth response and a 10-fold increased sensitivity to NGF. Neurite regeneration was significantly enhanced in both transfected subclones and, in contrast to untreated PC12 cells, could occur transiently in the absence of added NGF. These results suggest that GAP-43 may potentiate the action of NGF on neurite initiation and regeneration.
Brain Res Mol Brain Res 1990 Jan
PMID:Transfection of PC12 cells with the human GAP-43 gene: effects on neurite outgrowth and regeneration. 215 93

Growth-associated protein (GAP)-43 is a neuron-specific phosphoprotein whose expression is associated with axonal outgrowth during neuronal development and regeneration. In order to investigate the expression of this gene product in the early developing nervous system we have isolated and sequenced a cDNA for chicken GAP-43. 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. The cDNA hybridizes with two RNAs of differing molecular weights on Northern blots; both appear to be regulated similarly. These RNAs first appear in the brain on embryonic day 3 (E3), suggesting that GAP-43 begins to be expressed when neuroblasts become post-mitotic. 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.
Brain Res Mol Brain Res 1990 Jan
PMID:Chicken growth-associated protein (GAP)-43: primary structure and regulated expression of mRNA during embryogenesis. 215 95

Electrical stimulation of the Schaffer-collateral axonal system under conditions which do not elicit detectable seizure activity causes an increase in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine synthesis, in the hippocampus, olfactory cortex, neocortex and olfactory bulb. The degree of ODC activation is dependent upon the stimulus parameters. The results support the hypothesis that neuronal activity regulates hippocampal polyamine concentrations.
Brain Res Mol Brain Res 1990 Feb
PMID:Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo. 216 44

To investigate the potential role(s) of the insulin-like growth factors (IGFs) in embryogenesis, we have used in situ hybridization histochemistry to localize mRNAs for IGF-I, IGF-II, and the type I IGF receptor during an early period in rat embryonic development (embryonic days 14 and 15). IGF-I and IGF-II mRNAs were found in distinctly different patterns of cellular distribution. IGF-I mRNA was particularly abundant in undifferentiated mesenchymal tissue in the vicinity of sprouting nerves and spinal ganglia, and in circumscribed regions of the developing face that corresponded to the target zones of the trigeminal nerve. IGF-I mRNA was also found in aggregations of mesenchyme surrounding, but not in developing muscle and cartilage. IGF-I mRNA was selectively concentrated in areas of active tissue remodeling, such as the cardiac outflow tract, and was undetectable in liver, pituitary, and nervous system at this early stage of organogenesis. IGF-II mRNA was abundant in developing muscle, cartilage, and vascular tissue, and in the embryonic liver and pituitary. IGF-II mRNA was also conspicuous in areas of vascular interface with the brain, such as the choroid plexus and the organum vasculosum of the lamina terminalis. Messenger RNA for the type I IGF receptor was widely distributed in embryonic tissues, but the highest level were seen in the ventral floorplate of the hindbrain, where specialized neuroepithelial cells act as guides for axonal targeting. In conclusion, the different cellular patterns of expression of genes for IGF-I and IGF-II indicate that these two IGFs are differently regulated and, thus, may have significantly different roles in the process of embryonic development. Furthermore, the early and widespread expression of the type-I IGF receptor gene, in contrast to the relatively limited and localized pattern of IGF-I gene expression, is consistent with the view that this receptor may mediate the effects of IGF-II as well as IGF-I during embryogenesis.
Mol Endocrinol 1990 Sep
PMID:Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. 217 1

Horseradish peroxidase (HRP) injected into one lateral geniculate nucleus of male inbred PVG/Mol hooded rats is taken up by terminals of the optic nerve and transported retrogradely towards the opposite retina. Four hours after injection when a small portion of HRP had reached the retina, the eye and optic nerve were excised and incubated in vitro at 38 degrees C for another 3.5 hr during which the intraocular pressure (IOP) was set at 30 or 0 mmHg. During the in vitro period additional HRP entered the retina by axonal transport if the incubation medium contained enough Ca2+. Transport occurred at 0.45-1.1 mM Ca2+, but not at 0.30mM Ca2+. When transport occurred, no significant difference in degree of transport was found between the two pressures. The amount of HRP transported at 30 and 0 mmHg was very similar to that at 20 mmHg but significantly higher than that at 50 mmHg, (values at 20 and 50 mmHg from an earlier study). Thus, fast retrograde HRP transport was equally efficient at or near a physiological IOP as at zero pressure. Also, the degree of transport inhibition was not proportional to the height of the IOP, but started to increase above 30 mmHg. This is probably due to the presence of supporting tissue in the optic nerve head and inherent strength of the nerve fibers themselves. The lamina cribrosa in the rat eye is poorly developed and a shearing force on the nerve fibers due to laminar hole misalignment can largely be excluded. Effects on blood circulation are also excluded by the in vitro situation.
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PMID:Influence of low IOP and low calcium on retrograde axoplasmic transport in rat optic nerve in vitro. 242 Jun 29

The contribution of axonal activity to the ionic currents which generate bursting pacemaker activity was studied by using the two-electrode voltage-clamp technique in Aplysia bursting neuron somata in conjunction with intraaxonal voltage recordings. Depolarizing voltage-clamp pulses applied to bursting cell somata triggered axonal action potentials. The voltage-clamp current recording exhibited transient inward current "notches" corresponding to each of the axonal spikes. The addition of 50 microM tetrodotoxin (TTX) to the bathing medium blocked the fast axonal spikes and current notches, revealing a slower axonal spike which was blocked by the replacement of external Ca2+ with Co2+. The inward current evoked by applying a depolarizing voltage-clamp pulse in the soma is distorted by the occurrence of the axonal Ca2+ spike. Elimination of the axonal spike, by injecting hyperpolarizing current into the axon, changes both the time course and the magnitude of the inward current. The axonal Ca2+ spikes are followed by a series of Ca2+-dependent afterpotentials: a rapid postspike hyperpolarization, a depolarizing afterpotential (DAP) and, finally, a long-lasting postburst hyperpolarization. The long-lasting hyperpolarization is not blocked by 50 mM external tetraethyl ammonium, an effective blocker of Ca2+-activated K+ current [IK(Ca)], and does not appear to reverse at EK. Hence, the axonal long-lasting hyperpolarization may not be due to IK(Ca). Somatic voltage-clamp pulses in bursting neurons are followed by a slow inward tail current, which is sometimes coincident with a DAP in the axon. In some cells, the amplitude of the slow inward tail current is greatly reduced if axonal spikes and DAPs are prevented by hyperpolarization of the axon, while, in other cells, elimination of axonal activity has little effect. Therefore, the slow inward tail current is not necessarily an artifact of poor voltage-clamp control over the axonal membrane potential but probably results from the activation of an ionic conductance mechanism located partly in the axon and partly in the soma.
Cell Mol Neurobiol 1986 Sep
PMID:Axonal contribution to subthreshold currents in Aplysia bursting pacemaker neurons. 243 40

During regeneration of the optic nerve in goldfish, manipulations that disrupt the transmission of patterned visual information, if applied within the so-called 'sensitive period', lead to the formation of a diffuse retinotopic map (Schmidt, Cell. Mol. Neurobiol., 5 (1985) 65). The present study examined: (a) whether the sensitive period (14-50 days postcrush) coincides with the period in which specific 'growth-associated proteins' are present in the regenerating optic nerve terminals; and (b) whether manipulations that alter physiological activity during the sensitive period influence the expression of these proteins. Following bilateral optic nerve crush, goldfish regenerated their optic nerves either under normal illumination conditions (control), in total darkness, or with physiological activity suppressed in the nerve by intraocular injections of tetrodotoxin (TTX). At various times postcrush, proteins conveyed from the retina to the developing nerve endings were visualized by labeling the eye with [35S]methionine and then analyzing, by 2-dimensional gel electrophoresis and fluorography, radiolabeled proteins present in the optic tectum 15 h later. Rapidly-transported proteins that underwent large, specific increases during regeneration included the previously described 48 kDa growth-associated protein (GAP-48); labeling of GAP-48 was maximal during axonal outgrowth and then declined, but still remained well above background levels throughout the 'sensitive period'. Another group of rapidly-transported proteins, mol. wt. = 110-140 kDa (HMW), followed a similar time course, while levels of a 28 kDa protein peaked at 2 weeks and then declined rapidly. Thus, activity-dependent 'sharpening' processes occur during a period in which the levels of GAP-48 and HMW remain elevated in the nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity-dependent sharpening of the regenerating retinotectal projection in goldfish: relationship to the expression of growth-associated proteins. 244 16


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