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Query: UNIPROT:P06889 (Mol)
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The organization of the axonal cytoskeleton was investigated by analyzing the solubility and transport profile of the major cytoskeletal proteins in motor axons of the rat sciatic nerve under normal and regenerating conditions. When extracted with the Triton-containing buffer at low temperature, 50% of tubulin and 30% of actin were recovered in the insoluble form resistant to further depolymerizing treatments. Most of this cold-insoluble form was transported in slow component a (SCa), the slower of the two subcomponents of slow axonal transport, whereas the cold-soluble form showed a biphasic distribution between SCa and SCb (slow component b). Changes in slow transport during regeneration were studied by injuring the nerve either prior to (experiment I) or after (experiment II) radioactive labeling. In experiment I where the transport of proteins synthesized in response to injury was examined, selective acceleration of SCb was detected together with an increase in the relative proportion of this component. In experiment II where the response of the preexisting cytoskeleton was examined, a shift from SCa to SCb of the cold-soluble form was observed. The differential distribution and response of the two forms of tubulin and actin suggest that the cold-soluble form may be more directly involved in axonal transport.
Mol Neurobiol
PMID:Organization and slow axonal transport of cytoskeletal proteins under normal and regenerating conditions. 128 36

Rapid axonal transport is generally viewed as being exactly analogous to the secretory process in nonneuronal cells. The cell biology of rapid axonal transport is reviewed, the central concern being to explore those aspects that do not fit into the general secretory model and which may thus represent specific neuronal adaptations. Particular attention is paid to the relationship between the transport of newly synthesized proteins and of the membranous organelles that act as carriers. Sites in the transport sequence at which the behavior of axonal transport may differ from the secretory model are at the initiation of axonal transport at the trans-side of the Golgi apparatus, within the axon where molecules are deposited from the moving phase to a stationary phase, and at nerve terminals or axonal lesions where transport reversal takes place.
Mol Neurobiol
PMID:Relationships between the rapid axonal transport of newly synthesized proteins and membranous organelles. 128 35

The axonal transport of neurotransmitter receptors is thought to be a common phenomenon in many neuronal systems. The "machinery" for receptor (protein) "assembly" is found in the cell bodies of neurons and the "manufacture" of receptors takes place there. These receptors are then "shipped" to their ultimate destinations by a transport process. This is an axonal transport mechanism in the case of presynaptic receptors. Some form of transport process may also exist to send receptors out into the dendritic arborizations of neurons, although the latter is more difficult to verify. Axonal transport has been demonstrated, in the peripheral nervous system, for many different neurotransmitter receptors. In the central nervous system, the results are less clear, but indicate the presence of a transport mechanism for catecholamine, acetylcholine, and opiate sites. One important component then, in the development of receptors, is the transportation to terminal membrane sites where they are ultimately incorporated and available for interaction with neurotransmitters and drugs.
Mol Neurobiol
PMID:Transport of receptors. 128 37

Chronic exposure of rats to ethylene oxide (EO) causes distal axonal neuropathy of lumbosacral primary sensory neurons. To study the pathogenesis of this neuropathy, we measured rapid axonal transport in peripheral nerves. Rats were exposed for 6 h to 500 ppm EO in a chamber three times a wk for 15 wk. Rapid axonal transport and quantitative histological alterations of peripheral nerves were studied. After [35S]methionine injection into the dorsal root ganglion, the velocity of rapid anterograde axonal transport of radioisotope-labeled protein was measured. The velocity in the rats exposed to EO was 33% less than that in control rats exposed to filtered room air. However, histological differences were slight. Morphometric studies showed that in EO-exposed rats, only the distal portions of the sural nerve had significantly greater incidental degeneration of myelinated fibers than did controls. There were significantly fewer large myelinated fibers only in the distals peroneal nerve. Therefore, a decrease in the velocity of anterograde axonal transport, related to these slight histological abnormalities of the peripheral nerve, may play a causative role in the development of the distal axonal neuropathy owing to chronic EO exposure.
Mol Chem Neuropathol 1992 Dec
PMID:Rapid axonal transport velocity is reduced in experimental ethylene oxide neuropathy. 128 12

Gene expression of the axonal growth-associated protein, GAP-43, has been studied in the adult rat brain by in situ hybridization histochemistry. This protein is synthesized at high levels in neuronal somata in immature and regenerating neurons, but after establishment of mature synaptic relations its synthesis generally declines sharply, thus providing a marker denoting propensity for exhibiting synaptic plasticity. Detailed examination of the distribution of mRNA for GAP-43 in rat hippocampus is selectively and robustly expressed in the pyramidal neurons of field CA3 and, to a lesser extent, the polymorph neurons of the hilus of the dentate gyrus. Additional hippocampal regions of moderate expression include the tenia tecta and the subicular and entorhinal fields, but CA1 and CA2 are strikingly lower in signal. The significance of this pattern of localization is considered in the context of the phosphorylation of GAP-43 and its role in influencing synaptic events underlying the establishment and maintenance of long-term potentiation and plasticity in the hippocampus.
Brain Res Mol Brain Res 1992 Apr
PMID:GAP-43 mRNA localization in the rat hippocampus CA3 field. 131 99

The expression of the transcription factors Fos and Jun was studied in rat brain after transection of the fornix-fimbria (FF) using polyclonal antibodies to these proteins and immunocytochemical detection methods. FF-transection lead to a massive induction of Jun-like immunoreactivity (JLI) in neurons in the medial septal nucleus and in the vertical limb of the diagonal band of Broca, within 48 hours and lasting up to 14 days after lesion. Fos was not induced in these neurons after FF-transection. These results indicate that axotomized medial septal and diagonal band of Broca neurons selectively and rapidly express JLI. The role of Jun expression in axonal regeneration or neuronal death is discussed.
Brain Res Mol Brain Res 1992 Sep
PMID:Axotomized medial septal-diagonal band neurons express Jun-like immunoreactivity. 133 59

The hypoglossal nerve is a useful model system for analysis of gene expression in injured motoneurons. In particular, we sought to determine whether the increased appearance of the low affinity nerve growth factor receptor (p75NGFr) observed immunocytochemically following nerve injury can be directly correlated to increased levels of the p75NGFr mRNA. The present study also examined the relative effects of nerve crush versus nerve transection on the expression of p75NGFr mRNA. In sham-operated or intact animals, p75NGFr mRNA is detected rarely and then only at levels slightly higher than background. Following unilateral transection or crush of the rat hypoglossal nerve, the levels of p75NGFr mRNA increase in a time dependent fashion that parallels the appearance of the protein as reported previously. Moreover, this increase in p75NGFr mRNA following transection is dependent on a signal from the injured site, since blockage of axonal transport with vincristine also blocks the increased p75NGFr mRNA levels. When comparing the effect of nerve crush to nerve transection, we observed that the intensity of the response was greater in the crush paradigm versus that observed following transection. The duration of the response following nerve crush was shorter than that observed following transection of the nerve. The increase in p75NGFr mRNA after crush was most robust 4 days postlesion and appeared more robust primarily due to a 90-150% increased number of motoneurons expressing p75NGFr mRNA when compared to nerve transection. These data suggest that nerve crush is more effective than nerve transection in eliciting increased p75NGFr mRNA levels.
Brain Res Mol Brain Res 1992 Oct
PMID:Induction of nerve growth factor receptor (p75NGFr) mRNA within hypoglossal motoneurons following axonal injury. 133 83

The role of cAMP in the regulation of P0 gene expression was investigated in Schwann cells of normal, regenerated, and permanently transected rat sciatic nerve. Forskolin treatment of endoneurial segments of rat sciatic nerve resulted in increased cAMP and P0 mRNA levels in normal and regenerated nerves but not in permanently transected nerves, where axonal regeneration is prevented. This increase of cAMP and P0 mRNA occurred within 30 and 90 min, respectively. P0 mRNA levels in the endoneurial segment of the permanently transected nerve were not increased with dibutyryl cAMP. The Schwann cells of the permanently transected nerve, however, retained the ability to myelinate 15 embryonic day (E15) dorsal root ganglia (DRG) neuron and neurite networks cultured in vitro. P0 mRNA levels increased within 4 days in transected endoneurium segments cocultured with E15 DRG neurons and neurites and further increased in 21 day myelinating cocultures. Although cAMP was not detectable in 4 day cocultures, it increased to detectable levels in 21 day cultures, suggesting that cAMP is involved in the myelinating process. These results indicate that the presence of the axon is required for the observed increase of cAMP and P0 mRNA levels and suggest that the increase of cAMP occurs within the axon which then presumably activates a different Schwann cell second messenger pathway to induce P0 gene expression.
Brain Res Mol Brain Res 1992 Jan
PMID:P0 gene expression in Schwann cells is modulated by an increase of cAMP which is dependent on the presence of axons. 137 71

Dose- and term-dependent differences in the location and nature of brain lesions induced in rats and dogs by 2,5-hexanedione (2,5-HD), misonidazole, clioquinol, and acrylamide are reported. Subchronic neuropathies ("distal axonopathy") were induced by low-dose administration of these neurotoxicants and at high doses, lesions caused by acute or subacute neurotoxicity were found in the central nervous system (CNS). In rats, 2,5-HD induced extracellular edema, nerve cell degeneration, and axonal degeneration in the cerebellar and vestibular nuclei. Similar lesions were observed in misonidazole-treated dogs and clioquinol induced nerve cell degeneration in the hippocampus and malacia in the piriform lobes of these animals. In rats, acrylamide induced degeneration of Purkinje cells. Although the mechanism(s) underlying the differential neurotoxicity of high and low doses of these neurotoxicants remains unclear, we suggest certain biochemical mechanisms, cytotoxic edema and excitotoxicity, as factors in the production of such lesions after high-dose treatment.
Mol Chem Neuropathol
PMID:The same chemicals induce different neurotoxicity when administered in high doses for short term or low doses for long term to rats and dogs. 138 90

Since our characterization of the slit cDNA sequence, encoding a protein secreted by glial cells and involved in the formation of axonal pathways in Drosophila, we have discovered that the protein contains two additional sequence motifs that are highly conserved in a variety of proteins. A search of the GenPept database with the 73 amino acids at the carboxy terminus of slit revealed that this region contains significant similarity to a carboxy-terminal domain found in six other exported proteins. This observation has allowed us to define a new carboxy-terminal protein motif. In addition, comparisons with a 202 amino acid domain residing between epidermal growth factor (EGF) repeats in slit shows this region to be conserved in laminin, agrin and perlecan and, strikingly, also to lie between EGF repeats in both agrin and perlecan. Our analysis suggests this motif is involved in mediating interactions among extracellular proteins. Consistent with our previous characterization of the slit protein, both new motifs are found only in extracellular proteins. The identification of these two conserved motifs in slit reveals that the entire 1469 amino acids of the protein are made up of modular regions similar to those conserved in other extracellular proteins.
J Mol Biol 1992 Sep 20
PMID:Modularity of the slit protein. Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions. 140 56


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