Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schwann cells of the peripheral nervous system depend on the presence of both axons and basal lamina to achieve a myelinating phenotype. Furthermore, removal of axonal influence results in the cessation of myelination and down-regulation of myelin protein expression by Schwann cells. Here we examine whether both axons and basal lamina are required by Schwann cells for the expression of mRNA encoding the major myelin glycoprotein, P0. Cultures of Schwann cells and neurons obtained from dorsal root ganglia of 15 day embryonic rat pups were grown for up to 20 days in vitro under conditions that either allowed or prohibited basal lamina and myelin formation. These cultures were assayed for the expression of P0 mRNA by using an S1 nuclease-protection assay. After 20 days in vitro, the cultures that did not assemble basal lamina and that were incapable of myelin formation expressed P0 mRNA at a level which was comparable to that seen in identically aged, myelinating cultures. Both the myelinating and nonmyelinating cultures demonstrated an appreciable increase in P0 mRNA when compared to the starting embryonic dorsal root ganglia Schwann cells. The latter had a low, but detectable, level of mRNa for this myelin glycoprotein. The cultures that were devoid of basal lamina and myelin showed a clear increase in P0 mRNA by 11-15 days in culture. This increase in expression depended on the presence of neurons/neurites, since Schwann cells which were grown in neuron-depleted cultures expressed little, if any, P0 mRNA. In contrast to the levels of P0 mRNA, the nonmyelinating cultures had a significantly lower amount of P0 glycoprotein than did the cultures which assemble myelin. This suggests that the nonmyelinating Schwann cells regulate the level of this glycoprotein at the translational and/or the posttranslational level. The data presented here suggest that myelin protein mRNA expression and myelin assembly by Schwann cells are separable events, with the former depending on one or more neuronal/axonal factors.
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PMID:P0 mRNA expression in cultures of Schwann cells and neurons that lack basal lamina and myelin. 170 92

Independent transgenic mouse lines carrying the mouse Mos protooncogene linked to a retroviral transcriptional control sequence display behavioral abnormalities including circling, head tilting, and head bobbing. This dominant phenotype shows various degrees of penetrance in different transgenic founder animals and lines. Neuronal and axonal degeneration, gliosis, and inflammatory infiltrates are found in all transgenic mouse lines in which behavioral traits are present. Recordings of auditory-evoked potentials in mice of one of these lines demonstrate that transgenic mice are deaf; in these mice spiral ganglia degenerate and most of the cochlear hair cells are absent. By using an S1 nuclease protection assay, we have detected RNA expression of the transgene in all tissues examined and, in particular, at high levels in brain. In situ hybridization experiments show that Mos expression can be detected in specific areas of the central nervous system. Lesions are present in areas with demonstrable overexpression of Mos.
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PMID:Neuropathological changes in transgenic mice carrying copies of a transcriptionally activated Mos protooncogene. 170 18

The olfactory bulb of the rat contains chromogranin A at a similar level as the adrenal gland or the hypophysis as revealed by immunoblots. Olfactory chromogranin A also displays the same size as chromogranin A of endocrine cells. In the hippocampus and other brain regions, we could not detect chromogranin A by immunoblotting. In contrast, chromogranin A messenger ribonucleic acid (using S1 nuclease protection assays) was observed in all brain regions examined, including the olfactory bulb. By in situ hybridization histochemistry with a complementary ribonucleic acid probe (280 nucleotides), and by immunocytochemistry, chromogranin A synthesis could be localized to cell bodies of the mitral cell layer, of the external plexiform layer and of the periglomerular region of the olfactory bulb. Immunocytochemically, chromogranin A was also detected in the central projection areas of mitral and tufted cells in the primary olfactory cortex and the anterior amygdaloid area but not in the olfactory glomeruli, where the incoming olfactory nerve fibers of the primary olfactory neurons establish synaptic contacts. Taken together the data show that chromogranin A, following biosynthesis in the perikarya of the mitral and tufted cells, is specifically transported into their axonal terminals but not into their primary dendrites. We propose that the rat olfactory system could serve as a model for the study of chromogranin A regulation and function in neurons.
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PMID:Chromogranin A in the olfactory system of the rat. 209 16

The neural cell adhesion molecule (NCAM) is thought to be involved in several important events during CNS vertebrate development. This study provides additional information concerning the biochemical determination and anatomical localization of NCAM transcripts. Using S1 nuclease protection assays (S1-NPAs), NCAM transcripts in brain appear highest at birth, with NCAM messenger levels reduced some 20-fold by adulthood. By use of in situ hybridization, NCAM mRNA is demonstrated to be developmentally regulated in the cerebellum and hippocampus. The in situ hybridization findings, in addition to providing results to compare with past studies of NCAM immunolocalization, reveal that NCAM expression in dentate gyrus granule cells and cerebellar Purkinje cells is correlated with the final stages of axonal growth, e.g., synaptic stabilization. In situ hybridization demonstrates a developmental outside-to-inside gradient of NCAM transcripts in the dentate gyrus. Neurological mutant mice, reeler and stagger, provide evidence that NCAM expression is normal in the brain regions investigated, and does not correlate with the developmental perturbations present in these strains.
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PMID:NCAM gene expression during the development of cerebellum and dentate gyrus in the mouse. 233 83

Microinjection into an axon of an identified invertebrate neuron is shown to be a useful technique for analyzing the mechanisms of fast axonal transport. It permits direct assessment of the effect of agents that cannot permeate the plasma membrane on the translocation of material in the axon. The actin filament depolymerizer DNase I, when injected into the axon of the Aplysia neuron R2, caused a local block of fast transport of [3H]glycoprotein. Two agents that should interfere with the functioning of actin filaments without causing extensive depolymerization, tne N-ethylmaleimide-modified nuclease S1 fragment of myosin (injected) and dihydrocytochalasin B (applied externally). had no effect. Together these results suggest that actin plays a structural role in the axonal cytoskeleton rather than a role in transport force generation, the effect of DNase I being mediated by structural disordering of the axoplasm. Experiments were also done with inhibitors of dynein, the microtubule-associated ATPase. erythro-9-[3-(2-Hydroxynonyl)]adenine blocked transport but vanadate was ineffective.
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PMID:Microinjection into an identified axon to study the mechanism of fast axonal transport. 618 16

Microtubule-associated protein 1B (MAP1B) is a major constituent of the neuronal cytoskeleton that is expressed at high levels during early brain development and plays a role in axonal growth and neuronal plasticity. Previous studies suggested that the regulation of its gene expression is primarily at the transcriptional level. Thus, the characterization of the promoter region should help to define regulatory elements that control neuron-specific and developmental expression of the MAP1B gene. We have isolated genomic clones containing up to 11 kb of the upstream region of the rat MAP1B gene, sequenced approximately 1.8 kb upstream from the translation start codon, and identified several consensus sequences. These sequences include a consensus element common to several neuronal genes, a TCC repeat, a cAMP response element, and two TATA boxes that were 134 nucleotides apart from each other. S1 nuclease and RNase protection assays identified two corresponding groups of transcription initiation sites that were used selectively in distinct regions of the nervous system and during different stages of development. Transient transfection assays with neuronal and non-neuronal cell lines demonstrated that each TATA sequence and its corresponding adjacent region could independently direct neuron-specific expression of a reporter gene. Furthermore, the transcription of the reporter gene was initiated from the same sites as those of the MAP1B gene in vivo. These results suggest that two alternative and overlapping promoters, one inducible and the other constitutive, regulate the temporal and tissue-specific expression of the rat MAP1B gene.
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PMID:Two alternative promoters direct neuron-specific expression of the rat microtubule-associated protein 1B gene. 875 33