Primary structure and expression of β2: A novel subunit of neuronal nicotinic acetylcholine receptors

Deneris, Evan S.; Connolly, John G.; Boulter, Jim; Wada, Etsuko; Wada, Keiji; Swanson, Larry W.; Patrick, Jim; Heinemann, Sabine

doi:10.1016/0896-6273(88)90208-5

Cited by 292 publications

(113 citation statements)

References 30 publications

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“…The p2 subunit is a reliable indicator of cells expressing nicotinic AChR in the adult rat brain since it is required for a functional neuronal nicotinic cholinergic receptor. As previously reported (Deneris et al, 1988;Wada et al, 1989) the cRNA for the p2 subunit used in the present study labels cells broadly distributed across the CNS, reminiscent of the labeling pattern observed for agrin mRNA described above. However, differences between these patterns of hybridization were evident.…”

Section: Diencephalonsupporting

confidence: 48%

“…In some experiments, alternate sections were processed for in situ hybridization using ?S-labeled cRNA probes to localize mRNAs encoding either choline acetyltransferase (ChAT) (Lauterbom et al, 1993) or the p2 subunit of the nicotinic AChR (Deneris et al, 1988). Tissue sections were mounted on gelatin-coated slides following in situ hybridization, air dried, and exposed to B-Max hyperfilm (Amersham, Arlington Heights, IL) for 2-4 d. Mounted sections were subsequently defatted with chloroform, dipped in Kodak NTB2 emulsion (Eastman-Kodak, Rochester, NY), and exposed for 3-6 weeks at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions

et al. 1994

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Agrin is a protein implicated in the formation and maintenance of the neuromuscular junction.In addition to motor neurons, agrin mRNA has been detected in the brains of embryonic rat and chick and adult marine ray, suggesting that this molecule may also be involved in the formation of synapses between neurons. As a step toward understanding agrin's role in the CNS, we utilized Northern blot and in situ hybridization techniques to analyze the regional distribution and cellular localization of agrin mRNA in the spinal cord and brain of adult rats. The results of these studies indicate that the agrin mRNA is expressed predominantly by neurons broadly distributed throughout the adult CNS. Moreover, expression of agrin mRNA is not restricted to cholinergic structures or regions of the brain receiving cholinergic input. Recently, RNA isolated from rat embryonic spinal cord was shown to contain four alternatively spliced agrin mRNAs, referred to as agrin,, agrin,, agrin,,, and agrin,,, each of which encodes agrin proteins that are active in acetylcholine receptor aggregating assays (Ferns et al., 1992). Using the polymerase chain reaction we demonstrate that all four of these agrin transcripts are expressed within the adult CNS. Agrin,, agrin,, and agrin,, were present in all regions analyzed. In contrast, agrin,, was detected only in forebrain. Results of these studies indicate that both the level of expression and pattern of alternative splicing of agrin mRNA are differentially regulated in the brain. The broad and predominantly neuronal distribution of agrin mRNA in the adult brain suggests that, in addition to its role at the neuromuscular junction, agrin may play a role in formation and maintenance of synapses between neurons in the CNS.

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Section: Diencephalonsupporting

confidence: 48%

Section: Methodsmentioning

confidence: 99%

Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions

et al. 1994

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“…In the SCG10 gene, an NRSE is located farther upstream at position Ϫ1472 to Ϫ1452 (10), whereas in the NgCAM gene, five NRSEs have been discovered within the first intron (3). Furthermore, genes encoding the ␣ 1 -glycine receptor and the ␤2-subunit of the neuronal nicotinic acetylcholine receptor contain NRSEs in the 5Ј-untranslated region downstream of the transcriptional start site (11,12). It has been proposed that REST switches its activity from repressing to activating transcription when REST binds to an NRSE located in the 5Ј-untranslated region or less than 50 base pairs upstream from the TATA box (13).…”

Section: Re-1-silencing Transcription Factor (Rest)mentioning

confidence: 99%

Biological Activity and Modular Structure of RE-1-silencing Transcription Factor (REST), a Repressor of Neuronal Genes

Thiel¹,

Lietz²,

Cramer³

1998

Journal of Biological Chemistry

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The zinc finger protein RE-1-silencing transcription factor (REST) 1 is a transcriptional repressor that represses neuronal genes in nonneuronal tissues. Transfection experiments of neuroblastoma cells using a REST expression vector revealed that synapsin I promoter activity is controlled by REST. The biological activity of REST was further investigated using a battery of model promoters containing strong promoters/enhancers and REST binding sites. REST functioned as a transcriptional repressor when REST binding motifs derived from the genes encoding synapsin I, SCG10, ␣ 1 -glycine receptor, the ␤2-subunit of the neuronal nicotinic acetylcholine receptor, and the m4-subunit of the muscarinic acetylcholine receptor were present in the promoter region. No differences in the biological activity of these REST binding motifs tested were detected. Moreover, we found that REST functioned very effectively as a transcriptional repressor at a distance. Thus, REST represents a general transcriptional repressor that blocks transcription regardless of the location or orientation of its binding site relative to the enhancer and promoter. This biological activity could also be attributed to isolated domains of REST. Both repressor domains identified at the N and C termini of REST were transferable to a heterologous DNA binding domain and functioned from proximal and distal positions, similar to the REST protein. RE-1-silencing transcription factor (REST)1 , also known as neuron-restrictive silencer factor, functions as a transcriptional repressor of neuronal genes in nonneuronal tissues (1, 2). Target genes of REST are the genes encoding choline acetyltransferase, the type II sodium channel, SCG10, the m4 muscarinic acetylcholine receptor, and the adhesion proteins L1 and NgCAM (1-6). We have shown recently that the REST binding motif within the synapsin I promoter is responsible for restricting the expression of synapsin I to neuronal cells (7). Deletion of the REST binding site abolished neuron-specific expression of the reporter gene entirely, allowing constitutively acting elements of the promoter to direct expression in a nontissue specific manner.The REST binding motif termed the neural-restrictive silencer element (NRSE) was identified at various positions in those genes regulated by REST. NRSEs were found in the promoter region as shown for the synapsin I and the muscarinic acetylcholine receptor m4-subunit genes (7-9). In the SCG10 gene, an NRSE is located farther upstream at position Ϫ1472 to Ϫ1452 (10), whereas in the NgCAM gene, five NRSEs have been discovered within the first intron (3). Furthermore, genes encoding the ␣ 1 -glycine receptor and the ␤2-subunit of the neuronal nicotinic acetylcholine receptor contain NRSEs in the 5Ј-untranslated region downstream of the transcriptional start site (11,12). It has been proposed that REST switches its activity from repressing to activating transcription when REST binds to an NRSE located in the 5Ј-untranslated region or less than 50 base pairs upstream from the TATA bo...

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“…Acetylcholine is one of the excitatory neurotransmitters in the nervous system, and a family of neuronal nicotinic acetylcholine receptor (nAChR) genes has recently been identified. Ten different genes encoding neuronal nAChR subunits have been cloned and characterized in the chicken (a2 -(x8, nc I-naz3; Nef et al, 1988;Couturier et al, 1990a,b;Schoepfer et al, 1988Schoepfer et al, , 1990Hernandez,M.-C., in preparation) and in the rat (a2-a5, ,32-34; Boulter et al, 1986Boulter et al, , 1990Goldman et al, 1987;Wada et al, 1988;Deneris et al, 1988Deneris et al, , 1989Duvoisin et al, 1989;Isenberg and Meyer, 1989). Reconstitution studies in the Xenopus oocyte system have shown that the a2, a3 and a4 subunits can each lead to assembly of a functional nAChR in association with either na 1 or na3 and that each of these six receptors has specific physiological and pharmacological properties Wada et al, 1988;Bertrand et al, 1990;Couturier et al, 1990a).…”

Section: Introductionmentioning

confidence: 99%

Neuronal specificity of the alpha 7 nicotinic acetylcholine receptor promoter develops during morphogenesis of the central nervous system.

Matter-Sadzinski

Hernández²,

Roztocil³

et al. 1992

The EMBO Journal

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A transient transfection assay has been developed to analyse promoter activity in neuronal cells freshly dissociated from the chick central nervous system. The assay enabled us to identify cis-acting regulatory elements within the 5'-flanking region of the a7 nicotinic acetylcholine receptor gene. In differentiated retina, regulatory elements direct reporter gene expression to a small subset of neurons which has been identified as ganglion cells, i.e. to the population of neurons in which C7 transcripts were localized by in situ hybridization. However, these promoter elements exhibit ubiquitous activity in undifferentiated neural cells and in mesodermal stem cells. Our study supports the idea that c7 regulatory elements acquire their neuronal specificity in the course of embryogenesis.

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Primary structure and expression of β2: A novel subunit of neuronal nicotinic acetylcholine receptors

Cited by 292 publications

References 30 publications

Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions

Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions

Biological Activity and Modular Structure of RE-1-silencing Transcription Factor (REST), a Repressor of Neuronal Genes

Neuronal specificity of the alpha 7 nicotinic acetylcholine receptor promoter develops during morphogenesis of the central nervous system.

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