Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glial cell line-derived neurotrophic factor (GDNF), first characterized for its effect on dopamine uptake in central dopaminergic neurons, appears to be a powerful neurotrophic factor for motor neurons. GDNF has recently been shown to signal through a multisubunit receptor. This receptor is composed of a ligand-binding subunit, called GDNF receptor alpha (GDNFR alpha), and a signalling tyrosine kinase subunit, Ret. To gain further insight into GDNF function, we investigated the expression of GDNF and its receptors after nerve lesion in adult mice. Analysis of expression in muscle, nerve and spinal cord by RNase protection assay and in situ hydridization revealed that, in adult non-lesioned mice, GDNF mRNA was expressed in the nerve and GDNFR alpha mRNA in the nerve and the spinal cord, while the expression of Ret was restricted to spinal cord motor neurons. After a sciatic nerve crush a rapid increase in GDNF mRNA was observed in the distal part of the nerve and a delayed elevation in the muscle, while GDNFR alpha mRNA was up-regulated in the distal part of the sciatic nerve but not in proximal nerve or spinal cord. The lesion also induced a rapid increase in Ret mRNA expression, but the increase was observed only in spinal cord motor neurons and in dorsal root ganglion neurons. A pattern of expression of GDNF and its receptors similar to that seen after lesion in the adult was detected during embryonic development. Administration of GDNF enhanced sciatic nerve regeneration measured by the nerve pinch test. Taken together, these results suggest that GDNF has an important role during regeneration after nerve damage in the adult.
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PMID:Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. 924 Apr 2

We report the identification of an additional member of the glial cell line-derived neurotrophic factor (GDNF) family receptor, termed GFRalpha3, that is homologous to the previously identified GDNF and neurturin ligand binding receptors GFRalpha1 and GFRalpha2. GFRalpha3 is 32% and 37% identical to GFRalpha1 and GFRalpha2, respectively. RNase protection assays show that whereas gfralpha1 and gfralpha2 are abundant in both developing and adult brain, gfralpha3 is exclusively expressed during development. All receptors are widely present in both the developing and adult peripheral nervous system and in peripheral organs. For instance, in situ hybridization shows that the developing liver, stomach, intestine, kidney, and sympathetic chain, which all contain ret-expressing cells, transcribe unique complementary and overlapping patterns of most or all of the GDNF family receptors and ligands. In sensory neurons of the trigeminal ganglion gfralpha2 and gfralpha3 are expressed in different subpopulations of neurons, whereas gfralpha1 is coexpressed in some gfralpha2 and gfralpha3-positive neurons. We find that the gfralpha1 population of trigeminal neurons is absent in GDNF null mutant mice, suggesting that GDNF signals in vivo by interacting with GFRalpha1. Thus, our results show that there are at least three members in the GDNF family of ligand binding receptors and that these receptors may be crucial in conferring ligand specificity in vivo. The unique complementary and overlapping expression of gfralpha3 implies distinct functions in the developing and adult mouse from that of GFRalpha1 and GFRalpha2.
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PMID:Expression and regulation of GFRalpha3, a glial cell line-derived neurotrophic factor family receptor. 944 25

Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-alpha) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-alpha and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-alpha and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-alpha expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-alpha. This differential distribution of the GDNF receptor components (GDNFR-alpha and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.
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PMID:Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue. 1002 66

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) bind to GFR alpha-1 and GFR alpha-2 receptors, respectively, and their neurotrophic activity is mediated by the tyrosine kinase receptor, Ret. All these molecules were found to be expressed in primary cultures of rat glial cells, which were largely composed of astrocytes and maintained in serum-free medium. Although GDNF, NTN and Ret mRNA levels were at the limit of detection, RNase protection assays revealed relatively high amounts of GFR alpha-1 and GFR alpha transcripts. To characterize signals controlling their expression, glial cells were exposed to serum or treated with hormones acting through nuclear receptors and by activators of the cAMP or protein kinase C (PKC)-dependent pathways. Retinoic acid or 1,25-dihydroxyvitamin D3 appeared ineffective. In contrast, the 5-fold increase in GFR alpha-2 mRNA after 24 hr of treatment with 10(-10) M of tri-iodothyronine, suggests a physiological role of thyroid hormone in the regulation of this receptor in vivo. The serum induced a 7-fold increase in GFR alpha-1 mRNA levels. These changes may be mediated by the cAMP or PKC pathways because both forskolin and TPA up-regulated the GFR alpha-1 gene. Interestingly, only TPA led to a coordinated increase in the levels of GDNF, GFR alpha-1 and GFR alpha-2 mRNAs. On the other hand, NTN transcripts remained constant, irrespective of the culture conditions. Taken together, these results indicate that GDNF family ligands and their receptors are regulated in glial cells by common or independent transductional pathways, which could modulate their specific expression during brain development or in the case of trauma.
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PMID:Differential regulation of GDNF, neurturin, and their receptors in primary cultures of rat glial cells. 1131 68

The expression of mRNA for brain-derived neurotrophic factor (BDNF) is regulated by early visual experience. In this study, we sought to determine whether other neurotrophic factor mRNAs are similarly regulated. We reared pigmented rats from birth to postnatal day 21 in a normal light cycle, constant light (LR) or constant darkness (DR). In the retina, superior colliculus (SC), primary visual cortex (V1), hippocampus (HIPP) and cerebellum (CBL), using a ribonuclease protection assay (RPA), we examined expression of the mRNAs for nerve growth factor (NGF), BDNF, NT3, NT4, ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF). LR or DR alter the expression of the mRNAs for NGF, BDNF and NT3 and CNTF within the visual system. LR also upregulated BDNF mRNA expression within the cerebellum. In all of the structures examined, NT4 mRNA expression was unaltered by LR or DR and GDNF mRNA was undetectable. Notably, the same rearing condition could induce changes of opposite sign in the mRNA for a single factor in different structures or for different factors in the same structure. Thus, during developmental stages when sensory experience and neuroelectric activity are important in the shaping of visual circuitry, vision regulates the expression of multiple neurotrophic factor mRNAs and each mRNA has a unique profile with respect to the locus and sign of activity-induced changes.
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PMID:Complexity in the modulation of neurotrophic factor mRNA expression by early visual experience. 1285 94