Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ample evidence indicates that in nerve cells, several individual proteins are locally synthesized in postsynaptic domains in dendrites. By contrast, axonal terminals, at least in mammals, are generally thought to lack protein synthetic capacity. However, axonal nerve endings of the hypothalamo-neurohypophyseal tract have recently been shown to contain mRNAs encoding vasopressin, oxytocin, dynorphin, and neurofilament. In this report, we identify BC1 RNA, a small RNA polymerase III transcript that is specifically expressed in neurons, in hypothalamo-neurohypophyseal axons. BC1 RNA has previously been shown to be located in somatic and dendritic domains of various types of neurons in the rat nervous system. Here we present evidence to show that BC 1 RNA, like several neuropeptide mRNAs, is axonally transported from magnocellular hypothalamic neurons to neurosecretory nerve endings in the posterior pituitary. BC1 RNA, which has been reported to be a component of a ribonucleoprotein particle, is thus colocalized with dendritic mRNAs in dendritic domains and with axonal mRNAs in axonal domains, respectively. Such colocalization is indicative of functional interactions of BC1 RNA with those mRNAs that are targeted to extrasomatic domains of nerve cells.
...
PMID:Transport of BC1 RNA in hypothalamo-neurohypophyseal axons. 769 10

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.
...
PMID:PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas. 810 13

Brain cytoplasmic 1 (BC1) RNA is a small non-translated RNA polymerase III transcript. Because this RNA can be detected in the rat posterior pituitary with 35S in situ hybridization autoradiography, it has been hypothesized that this RNA might be transported in the axons of hypothalamo-neurohypophyseal neurons. In the present study, we aimed to determine the cellular localization of BC1 more precisely by using non-radioactive in situ hybridization of BC1 RNA at both the light and electron microscopic levels. Our studies revealed that BC1 RNA was indeed located intra-axonally. Furthermore, BC1 RNA was abundant within a subset of axonal swellings and/or terminals, and was also found in discrete cytoplasmic domains of undilated axonal segments. Using a semiquantitative in situ hybridization approach, we have measured and compared the changes in BC1 RNA and arginine vasopressin (AVP) mRNA during dehydration (chronic salt-loading) and rehydration. Chronic salt-loading significantly increased both BC1 RNA and AVP mRNA. The increase in BC1 RNA labelling (2.5-fold), however, was modest and somewhat less enduring than the increase in AVP mRNA labelling (13-fold). Upon rehydration, both the BC1 and vasopressin transcripts in the posterior pituitary rapidly returned to control values. In conclusion, like vasopressin mRNA, BC1 RNA is transported in axons of the hypothalamo-neurohypophyseal system where it aggregates in a subset of axonal swellings, and its axonal transport is similarly regulated. Therefore, we propose that BC1 RNA might be involved in the axonal targeting, docking and/or transport of AVP or other axonal mRNAs.
...
PMID:BC1 RNA and vasopressin mRNA in rat neurohypophysis: axonal compartmentalization and differential regulation during dehydration and rehydration. 856 74

In peripheral nerves, ciliary neurotrophic factor (CNTF) is localized to a subset of Schwann cells and is decreased in synthesis during Wallerian degeneration. This pattern of expression is similar to that of myelin protein genes. In the present study, C57BL/Wld mice, which exhibit delayed Wallerian degeneration, were used to determine the role of axonal contact on the regulation of CNTF synthesis. Western blot analysis showed that CNTF immunoreactivity in Wld nerves remained almost normal even 10 days after ligation when it was almost undetectable in control mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that 4 days after ligation, concentrations of CNTF mRNA in Wld mice had decreased much less than in control mice, but that at 10 days CNTF mRNA concentrations in Wld and control mice were comparably low. These observations suggest that maintenance of axonal contact in the absence of axonal transport from the cell body delays the decrease of CNTF mRNA normally seen after injury. Also, during Wallerian degeneration in Wld mice, the decrease of CNTF protein is delayed for many days longer than the decrease in CNTF mRNA.
...
PMID:Delay of CNTF decrease following peripheral nerve injury in C57BL/Wld mice. 930 77

Functional chemokine receptors and chemokines are expressed by glial cells within the CNS, though relatively little is known about the patterns of neuronal chemokine receptor expression and function. We developed monoclonal antibodies to the CCR1, CCR2, CCR3, CCR6, CXCR2, CXCR3 and CXCR4 chemokine receptors to study their expression in human fetal neurons cultured from brain tissue as well as the clonally derived NT2.N human neuronal cell line (NTera 2/cl.D1). Specific monoclonal antibody labeling demonstrated expression of CCR2, CXCR2, CXCR3 and CXCR4 on neurons from both sources. Co-labeling studies revealed strong expression of CXCR3 and CXCR4 on both dendritic and axonal processes, with a weaker expression of CXCR2 and CCR2. Reverse transcriptase-polymerase chain reaction analysis of pure NT2.N neurons confirmed RNA expression for CCR2, CXCR2, CXCR3 and CXCR4. No changes in the neuronal labeling pattern of chemokine receptor expression were noted when NT2.N neurons were grown on a supporting layer of astrocytes, again consistent with similar patterns seen in primary human fetal brain cultures. Analysis of single-cell calcium transients revealed a robust response to stromal derived factor-1alpha (CXCR4) and melanocyte growth-stimulating activity (CXCR2), and variable response to monocyte chemoattractant protein-1 (CCR2) or interferon-gamma inducible protein-10 (CXCR3). Finally, we detected the release of monocyte chemoattractant protein-1 from pure cultures of NT2.N neurons, but not undifferentiated NT2 cells. These data indicate that individual neurons may not only co-express multiple functional chemokine receptors, but also that neurons themselves produce chemokines which may influence cellular function within the central nervous system.
...
PMID:Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons. 1082 41

In neurons, localized RNAs have been identified in dendrites and axons; however, RNA transport in axons remains poorly understood. Here we analyzed axonal RNA transport in goldfish Mauthner neurons in vivo. BC1 RNA, a noncoding RNA polymerase III transcript that is targeted to dendrites in neurons of the rodent nervous system, was used as a probe for axonal RNA transport. Somata of Mauthner neurons were microinjected with various RNAs. Full-length BC1 RNA, but not control RNAs of similar length, was targeted to both axons and dendrites of Mauthner neurons. BC1 RNA was transported in the form of a rapidly advancing wave front that progressed along axons, in a microtubule-dependent manner, at a rate of 2 micrometer/sec. Whereas a BC1 5' segment of 65 nucleotides was transported to axons and dendrites in a way indistinguishable from full-length BC1 RNA, a BC1 3' segment of 60 nucleotides did not enter Mauthner cell processes to any significant extent. In the wake of the wave advancing through the axon, BC1 RNA was found localized to discrete, spatially delimited domains at the axonal surface. Such demarcated cortical concentrations of BC1 RNA could not be observed after disruption of F-actin organization in the axon. It is concluded that the specific delivery of BC1 RNA to spatially defined axonal target sites is a two-step process that requires the sequential participation of microtubules for long-range axial transport and of actin filaments for local radial transfer and focal accumulation in cortical domains.
...
PMID:Transport of Neuronal BC1 RNA in Mauthner Axons. 1204 34

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats. In the intact brain, the V1a receptor was expressed in neurons located in all layers of the frontoparietal cortex. The V1a receptor-immunoreactive product was predominantly localized to neuronal nuclei and had both a diffused and punctate staining pattern. The V1a receptors were also expressed in astrocytes, especially in layer 1 of the frontoparietal cortex. In these cells, two distinctive patterns of immunopositive staining for V1a receptors were observed: a diffused cytosolic staining of cell bodies and processes and a clearly punctate staining pattern that was predominantly localized to the astrocytic cell bodies. The real-time reverse-transcriptase polymerase chain reaction analysis of changes in mRNA for the V1a receptor demonstrated that after TBI, there is an early (4 h post-TBI) increase in the number of transcripts in the ipsilateral frontoparietal cortex, when compared to the contralateral hemisphere or the sham-injured rats. This increase in the message was followed by the up-regulation of expression of the V1a receptors at the protein level. This was most evident in cortical astrocytes in the areas surrounding the lesion. The number of the V1a receptor-immunopositive astrocytes in the traumatized parenchyma gradually increased, starting at 8 h and peaking at 4-6 days after TBI. Furthermore, a redistribution of V1a receptors from the astrocytic cell bodies to the astrocytic processes was observed. In addition to astrocytes, an increased expression of V1a receptors was found in the endothelium of both blood microvessels and the large-diameter blood vessels in the frontoparietal cortex ipsilateral to injury. This increase in the V1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1-2 h following the impact, there was also a striking increase in the number of the V1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.
...
PMID:Increased expression of vasopressin v1a receptors after traumatic brain injury. 1531 8

Although male reproductive function is primarily androgen dependent, many studies suggest that estrogens have direct actions on the male reproductive organs. Pelvic autonomic neurons provide the motor control of the internal reproductive organs and the penis and various properties of these neurons are affected by endogenous androgens. However, the possible role of estrogens at this site has not been examined. Here we have investigated the significance of estrogens produced by aromatization of testosterone (T) in the physiological actions of androgens on adult male rat pelvic ganglion neurons. Reverse transcriptase polymerase chain reaction (RT-PCR) studies showed that aromatase and both estrogen receptors (ERalpha and ERbeta) are expressed in these ganglia. Western blotting also showed that aromatase is expressed in male pelvic ganglia. Using immunohistochemical visualization, ERalpha was predominantly expressed by nitric oxide synthase (NOS)-positive parasympathetic pelvic ganglion neurons. In vivo studies showed that the decrease in pelvic ganglion soma size caused by gonadectomy could be prevented by administration of T or dihydrotestosterone (DHT), but not 17beta-estradiol (E2), showing that this maintenance action of testosterone is mediated entirely by androgenic mechanisms. However, in vitro studies of cultured pelvic ganglion neurons revealed that T, DHT and E each stimulated the growth of longer and more complex neurites in both noradrenergic and cholinergic NOS-expressing neurons. The effects of T were attenuated by either androgen or estrogen receptor antagonists, or by inhibition of aromatase. Together these studies demonstrate that estrogens are likely to be synthesized in the male pelvic ganglia, produced from T by local aromatase. The effects of androgens on axonal growth are likely to be at least partly mediated by estrogenic mechanisms, which may be important for understanding disease-, aging- and injury-induced plasticity in this part of the nervous system.
...
PMID:Androgen and estrogen receptor-mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia. 1762 10

Extracellular ATP facilitates the release of dopamine via P2 receptor activation in parts of the mesolimbic system. To characterize P2X/Y receptor subtypes in the developing dopaminergic system, their expression in organotypic slice co-cultures including the ventral tegmental area/substantia nigra (VTA/SN) complex and the prefrontal cortex (PFC) was studied in comparison to the receptor expression in 3-5 day-old and adult rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) with specific primers for the P2X(1,2,3,4,6,7) and P2Y(1) receptors in the tissue extracts of organotypic co-cultures revealed the presence of the P2X and P2Y receptor mRNAs investigated. Multiple immunofluorescence labeling of the P2X/Y receptor protein indicated differences in the regional expression in the organotypic co-cultures after 10 days of cultivation (VTA/SN, P2X(1,2,3,4,6,7), P2Y(1,6,12); PFC, P2X(1,3,4,6,7), P2Y(1,2,4,6,12)). At postnatal days 3-5, an immunofluorescence mostly comparable to that of adult rats was observed (VTA/SN and PFC: P2X(1,2,3,4,6,7), P2Y(1,2,4,6,12)). There was one important exception: the P2X(7) receptor immunocytochemistry was not found in adult tissue, suggesting a potential role of this receptor in the development. Only few P2 receptors (e.g. P2X(1), P2Y(1)) were expressed at fibers interconnecting the dopaminergic VTA/SN with the PFC in the organotypic co-cultures. The treatment of the cultures with the ATP analogues 2-methylthio-ATP and alpha,beta-methylene-ATP induced an increase in axonal outgrowth and fiber density, which could be inhibited by pre-treatment with the P2X/Y receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid. The co-localization of the dopamine-(D1) receptor with the P2X(1) receptor in organotypic slice cultures was evident. In the PFC of the co-cultures, and that of young but not adult rats, a number of tyrosine hydroxylase (TH)-positive cells also possessed P2Y(1)-immunoreactivity (IR). Additionally, a strong P2Y(1)-IR was observed on astrocytes. The present results show a time-, region- and cell type-dependent in vitro and in vivo expression pattern of different P2 receptor subtypes in the dopaminergic system indicating the involvement of ATP and its receptors in neuronal development and growth.
...
PMID:P2 receptor expression in the dopaminergic system of the rat brain during development. 1786 6

Amyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both candidate gene and genome-wide studies, but the genetic causes remain largely unknown. We have performed two independent parallel studies, both implicating the RNA polymerase II component, ELP3, in axonal biology and neuronal degeneration. In the first, an association study of 1884 microsatellite markers, allelic variants of ELP3 were associated with ALS in three human populations comprising 1483 people (P=1.96 x 10(-9)). In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: -0.49, P=1.83 x 10(-12) (start codon morpholino) and -0.46, P=4.05 x 10(-9) (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P=0.01). These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS.
...
PMID:Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. 1899 18


1 2 Next >>

---