Regulation of gene expression by muscarinic acetylcholine receptors

In the brain, muscarinic acetylcholine receptors (mAChRs) are involved in higher cognitive functions including synaptic plasticity and memory. In Alzheimer's disease (AD) patients the cholinergic nervous system is severely damaged. In order to reinforce the cholinergic system, clinical tests were started to use cholinomimetic drugs to treat AD patients. To identify the genes involved in mAChR signalling, we used a differential display approach and found 11 genes that were readily activated by mAChR with 1 hour of activation. These included the transcription factors Egr-1, Egr-2, Egr-3, c-Jun, Jun-D and Gos-3; the growth regulator hCyr61; the signalling factors NGFi-B (nerve growth factor induced gene-B) and Etr101; the unknown gene Gig-2 (for G-protein-coupled receptor induced gene 2); and the acetylcholinesterase gene (ACHE). Our data show that multiple immediate-early genes are under the control of mAChRs, and they suggest that these genes play important roles in coupling receptor stimulation to long-term neuronal responses. The results also suggest a feedback mechanism where up-regulated ACHE expression and accelerated breakdown of acetylcholine (ACh) at the cholinergic synapses limits increases in cholinergic transmission. Three hours after m1 mAChR activation a different pattern of gene expression was demonstrated. It included the novel genes Gig-3 and Gig-4, as well as the LIM-only protein LM04. Like ACHE, these genes are target genes which may be under the control of the above immediate-early genes. Together, our data show that muscarinic receptors induce a complex and sustained pattern of gene expression that may be involved in the regulation of cholinergic transmission as well as the control of cellular functions in post-synaptic cholinergic target cells. These results may contribute to a better understanding of the effects and side effects of cholinomimetic treatment in AD patients.

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Regulation of Gene Expression by Muscarinic Acetylcholine Receptors: A Comprehensive Approach for the Identification of Regulated Genes

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2000.tb06939.x ◽

2006 ◽

Vol 920 (1) ◽

pp. 305-308

Author(s):

HEINZ KAMMER ◽

MANUEL MAYHAUS ◽

CLAUDIA ALBRECHT ◽

BARBARA ANDRESEN ◽

JAROSLAV KLAUDINY ◽

...

Keyword(s):

Gene Expression ◽

Acetylcholine Receptors ◽

Regulation Of Gene Expression ◽

Comprehensive Approach ◽

Muscarinic Acetylcholine Receptors ◽

Muscarinic Acetylcholine

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Regulation of gene expression by muscarinic acetylcholine receptors

Biochemical Society Transactions ◽

10.1042/bst028a017 ◽

2000 ◽

Vol 28 (1) ◽

pp. A17-A17

Author(s):

R.M. Nitsch ◽

C. Albrecht ◽

M. Mayhaus ◽

B. Hoffmann ◽

C. Demiralay ◽

...

Keyword(s):

Gene Expression ◽

Acetylcholine Receptors ◽

Regulation Of Gene Expression ◽

Muscarinic Acetylcholine Receptors ◽

Muscarinic Acetylcholine

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Roles of Genes 44, 50, and 51 in Regulating Gene Expression and Host Takeover during Infection of Bacillus subtilis by Bacteriophage SPO1

Journal of Bacteriology ◽

10.1128/jb.186.6.1785-1792.2004 ◽

2004 ◽

Vol 186 (6) ◽

pp. 1785-1792 ◽

Cited By ~ 15

Author(s):

Aruna Sampath ◽

Charles R. Stewart

Keyword(s):

Gene Expression ◽

Protein Synthesis ◽

Bacillus Subtilis ◽

Regulation Of Gene Expression ◽

Immediate Early Genes ◽

Early Gene ◽

Immediate Early ◽

Triple Mutant ◽

Early Genes ◽

Rna And Protein Synthesis

ABSTRACT We show that the products of SPO1 genes 44, 50, and 51 are required for the normal transition from early to middle gene expression during infection of Bacillus subtilis by bacteriophage SPO1; that they are also required for control of the shutoff of host DNA, RNA, and protein synthesis; and that their effects on host shutoff could be accounted for by their effects on the regulation of gene expression. These three gene products had four distinguishable effects in regulating SPO1 gene expression: (i) gp44-50-51 acted to restrain expression of all SPO1 genes tested, (ii) gp44 and/or gp50-51 caused additional specific repression of immediate-early genes, (iii) gp44 and/or gp50-51 stimulated expression of middle genes, and (iv) gp44 and/or gp50-51 stimulated expression of some delayed-early genes. Shutoff of immediate-early gene expression also required the activity of gp28, the middle-gene-specific sigma factor. Shutoff of host RNA and protein synthesis was accelerated by either the 44− single mutant or the 50−51− double mutant and more so by the 44−50−51− triple mutant. Shutoff of host DNA synthesis was accelerated by the mutants early in infection but delayed by the 44−50−51− triple mutant at later times. Although gp50 is a very small protein, consisting almost entirely of an apparent membrane-spanning domain, it contributed significantly to each activity tested. We identify SPO1 genes 41 to 51 and 53 to 60 as immediate-early genes; genes 27, 28, and 37 to 40 as delayed-early genes; and gene 52 as a middle gene.

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Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4

Molecular and Cellular Biology ◽

10.1128/mcb.5.8.1997-2008.1985 ◽

1985 ◽

Vol 5 (8) ◽

pp. 1997-2008 ◽

Cited By ~ 4

Author(s):

N A DeLuca ◽

P A Schaffer

Keyword(s):

Gene Expression ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Immediate Early Genes ◽

Early Gene ◽

Immediate Early ◽

Temperature Sensitive ◽

Wild Type ◽

Early Genes ◽

Simplex Virus

To better define the activities on herpes simplex virus type 1 gene expression of temperature-sensitive and wild-type forms of the transcriptional regulatory protein ICP4, regulatory sequences from immediate-early, early, and late herpes simplex virus genes were fused to the gene for chloramphenicol acetyltransferase (CAT). These constructs were used in trans induction and cotransfection experiments with wild-type and temperature-sensitive mutant alleles of ICP4. The ICP4 genes used in this study were cloned from the KOS strain (wild type) and two phenotypically distinct temperature-sensitive ICP4 mutants, tsB32 and tsL14 (DeLuca et al., J. Virol. 52:767-776, 1984), both alone and in conjunction with three other immediate-early genes. The latter series of plasmids was used to assess the influence of additional immediate-early gene products on gene expression in the presence of a given ICP4 allele. The results of this study demonstrate that the phenotypes of these ICP4 mutants observed in cell culture at the nonpermissive temperature were determined in part by activities associated with the mutant ICP4 polypeptides and that these activities differed from those of wild-type ICP4. Low levels of wild-type ICP4 had a marginal but reproducible stimulatory effect on immediate-early CAT gene expression, especially the pIE4/5CAT chimera. This effect was diminished with increasing quantities of ICP4, suggesting an inhibitory role for the wild-type form of the protein. The ICP4 mutants had a strong stimulatory effect on immediate-early CAT expression, consistent with their phenotypes at 39 degrees C. The mutant forms of the ICP4 polypeptide differed in their ability to induce CAT activity from an early chimeric gene. Thus, the tsL14 form of ICP4 was effective in early gene induction (i.e., ptkCAT was induced), whereas the ICP4 derived from tsB32 was slightly inhibitory. Cotransfection of tsB32 ICP4 simultaneously with other immediate-early genes resulted in a marginal increase in ptkCAT induction. This induction was enhanced when the gene for ICP4 was inactivated by restriction enzyme cleavage, substantiating the inhibitory effect of the tsB32 form of ICP4. The two mutant ICP4 genes (tsB32 and tsL14) were unable to trans-activate either of the late CAT constructs (p5CAT and pL42CAT) tested. Cotransfecting tsL14 ICP4 with the other immediate-early genes resulted in activation of p5CAT but not pL42CAT. Taken together, these studies demonstrate that (i) low levels of wild-type ICP4 have stimulatory effect on immediate-early promoters and that higher concentrations of wild-type ICP4 have an inhibitory effect on these promoters, (ii) isolated mutant form of ICP4 exhibit activities that reflect the phenotypes of the mutants from which they were isolated, and (iii) immediate-early gene products other than ICP4 are involved in determining the distinct phenotypes of the two mutants at 39 degrees Celsius.

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Calcium Signaling and c-Fos Gene Expression via M3 Muscarinic Acetylcholine Receptors in Human T- and B-Cells

The Japanese Journal of Pharmacology ◽

10.1254/jjp.84.124 ◽

2000 ◽

Vol 84 (2) ◽

pp. 124-132 ◽

Cited By ~ 38

Author(s):

Takeshi Fujii ◽

Koichiro Kawashima

Keyword(s):

Gene Expression ◽

B Cells ◽

Calcium Signaling ◽

Acetylcholine Receptors ◽

Muscarinic Acetylcholine Receptors ◽

T And B Cells ◽

Muscarinic Acetylcholine

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LINC00473 as an Immediate Early Gene under the Control of the EGR1 Transcription Factor

Non-Coding RNA ◽

10.3390/ncrna6040046 ◽

2020 ◽

Vol 6 (4) ◽

pp. 46

Author(s):

Vincenza Aliperti ◽

Emilia Vitale ◽

Francesco Aniello ◽

Aldo Donizetti

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Immediate Early Genes ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Secondary Response ◽

Early Genes ◽

Regulatory Cascade ◽

Non Coding Rnas

Immediate early genes play an essential role in cellular responses to different stimuli. Many of them are transcription factors that regulate the secondary response gene expression. Non-coding RNAs may also be involved in this regulatory cascade. In fact, they are emerging as key actors of gene expression regulation, and evidence suggests that their dysregulation may underly pathological states. We previously took a snapshot of both coding and long non-coding RNAs differentially expressed in neuronal cells after brain-derived neurotrophic factor stimulation. Among these, the transcription factor EGR1 (a well-known immediate early gene) and LINC00473 (a primate-specific long non-coding RNA) that has emerged as an interesting RNA candidate involved in neuronal function and in cancer. In this work, we demonstrated that LINC00473 gene expression kinetics resembled that of immediate early genes in SH-SY5Y and HEK293T cells under different cell stimulation conditions. Moreover, we showed that the expression of LINC00473 is under the control of the transcription factor EGR1, providing evidence for an interesting functional relationship in neuron function.

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