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Gene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells.

In maturing postnatal cerebellar granule cells, the Etv1/Er81 transcription factor is induced by sequential activity-dependent mechanisms through stimulation of AMPA and NMDA receptors, voltage-dependent Nav1.2 [Na.sup.+] channels, and voltage-dependent [Ca.sup.2+] channels. Etv1 then up-regulates a... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America May 29, 2012, Vol.109(22), pp.8734-8739
Main Author: Abe, Haruka
Other Authors: Okazawa, Makoto , Nakanishi, Shigetada
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1206418109
Link: http://search.proquest.com/docview/1017989665/?pq-origsite=primo
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title: Gene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells.
format: Article
creator:
  • Abe, Haruka
  • Okazawa, Makoto
  • Nakanishi, Shigetada
subjects:
  • Animals–Pharmacology
  • Base Sequence–Cytology
  • Brain-Derived Neurotrophic Factor–Metabolism
  • Cell Line, Tumor–Genetics
  • Cells, Cultured–Metabolism
  • Cerebellum–Genetics
  • DNA-Binding Proteins–Metabolism
  • Extracellular Signal-Regulated MAP Kinases–Drug Effects
  • Gene Expression Regulation–Genetics
  • Guanine Nucleotide Exchange Factors–Metabolism
  • Immunoblotting–Genetics
  • Luciferases–Metabolism
  • Mice–Drug Effects
  • Mice, Inbred Icr–Genetics
  • Mutation–Genetics
  • Phosphorylation–Metabolism
  • Promoter Regions, Genetic–Genetics
  • RNA Interference–Metabolism
  • Receptor, Trkb–Genetics
  • Receptors, N-Methyl-D-Aspartate–Metabolism
  • Reverse Transcriptase Polymerase Chain Reaction–Genetics
  • Serine–Metabolism
  • T-Lymphoma Invasion and Metastasis-Inducing Protein 1–Genetics
  • Threonine–Metabolism
  • Transcription Factors–Metabolism
  • Brain-Derived Neurotrophic Factor
  • DNA-Binding Proteins
  • Etv1 Protein, Mouse
  • Guanine Nucleotide Exchange Factors
  • Nr2c Nmda Receptor
  • Receptors, N-Methyl-D-Aspartate
  • T-Lymphoma Invasion and Metastasis-Inducing Protein 1
  • Tiam1 Protein, Mouse
  • Transcription Factors
  • Threonine
  • Serine
  • Luciferases
  • Receptor, Trkb
  • Extracellular Signal-Regulated MAP Kinases
ispartof: Proceedings of the National Academy of Sciences of the United States of America, May 29, 2012, Vol.109(22), pp.8734-8739
description: In maturing postnatal cerebellar granule cells, the Etv1/Er81 transcription factor is induced by sequential activity-dependent mechanisms through stimulation of AMPA and NMDA receptors, voltage-dependent Nav1.2 [Na.sup.+] channels, and voltage-dependent [Ca.sup.2+] channels. Etv1 then up-regulates a battery of maturation genes involved in the cerebellar circuitry. In this process, BDNF is also induced and participates in the up-regulation of these maturation genes. Using cultures of granule cells, we addressed how the activity-dependent and BDNF signaling mechanisms converge on the regulation of the representative NR2C NMDA receptor and Tiam1 maturation genes. BDNF up-regulated both the NR2C and Tiara1 genes via the TrkB-Erk cascade and this up-regulation was blocked not only by inhibition of the activity-dependent signaling mechanisms but also by suppression of Etv1 expression with Etv1 siRNA. Importantly, Etv1 was selectively phosphorylated by Erk1/2 in the BDNF signaling cascade, and the inhibition of this phosphorylation abrogated the BDNF-induced up-regulation of the NR2C and Tiam1 genes. The luciferase reporter assays in combination with mutations of MEK and Etv1 indicated that the Erk-mediated, phosphorylated Etv1 interacted with the Ets motifs of the NR2C promoter sequence and that phosphorylation at both serine 94 and a cluster of threonines and a serine (Thr139, Thr143, and Ser146) of Etv1 was indispensable for the BDNF-mediated activation of the NR2C promoter activity. This study demonstrates that the NR2C and Tiara1 maturation genes are synergistically controlled by the activity-dependent induction of Etv1 and its phosphorylation by the BDNF signaling cascade. activity-dependent regulation | cell culture | cerebellum | protein modification | synaptic maturation doi/10.1073/pnas.1206418109
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1206418109
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleGene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells.
creatorAbe, Haruka ; Okazawa, Makoto ; Nakanishi, Shigetada
contributorAbe, Haruka (correspondence author) ; Abe, Haruka (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, May 29, 2012, Vol.109(22), pp.8734-8739
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1206418109
subjectAnimals–Pharmacology ; Base Sequence–Cytology ; Brain-Derived Neurotrophic Factor–Metabolism ; Cell Line, Tumor–Genetics ; Cells, Cultured–Metabolism ; Cerebellum–Genetics ; DNA-Binding Proteins–Metabolism ; Extracellular Signal-Regulated MAP Kinases–Drug Effects ; Gene Expression Regulation–Genetics ; Guanine Nucleotide Exchange Factors–Metabolism ; Immunoblotting–Genetics ; Luciferases–Metabolism ; Mice–Drug Effects ; Mice, Inbred Icr–Genetics ; Mutation–Genetics ; Phosphorylation–Metabolism ; Promoter Regions, Genetic–Genetics ; RNA Interference–Metabolism ; Receptor, Trkb–Genetics ; Receptors, N-Methyl-D-Aspartate–Metabolism ; Reverse Transcriptase Polymerase Chain Reaction–Genetics ; Serine–Metabolism ; T-Lymphoma Invasion and Metastasis-Inducing Protein 1–Genetics ; Threonine–Metabolism ; Transcription Factors–Metabolism ; Brain-Derived Neurotrophic Factor ; DNA-Binding Proteins ; Etv1 Protein, Mouse ; Guanine Nucleotide Exchange Factors ; Nr2c Nmda Receptor ; Receptors, N-Methyl-D-Aspartate ; T-Lymphoma Invasion and Metastasis-Inducing Protein 1 ; Tiam1 Protein, Mouse ; Transcription Factors ; Threonine ; Serine ; Luciferases ; Receptor, Trkb ; Extracellular Signal-Regulated MAP Kinases
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descriptionIn maturing postnatal cerebellar granule cells, the Etv1/Er81 transcription factor is induced by sequential activity-dependent mechanisms through stimulation of AMPA and NMDA receptors, voltage-dependent Nav1.2 [Na.sup.+] channels, and voltage-dependent [Ca.sup.2+] channels. Etv1 then up-regulates a battery of maturation genes involved in the cerebellar circuitry. In this process, BDNF is also induced and participates in the up-regulation of these maturation genes. Using cultures of granule cells, we addressed how the activity-dependent and BDNF signaling mechanisms converge on the regulation of the representative NR2C NMDA receptor and Tiam1 maturation genes. BDNF up-regulated both the NR2C and Tiara1 genes via the TrkB-Erk cascade and this up-regulation was blocked not only by inhibition of the activity-dependent signaling mechanisms but also by suppression of Etv1 expression with Etv1 siRNA. Importantly, Etv1 was selectively phosphorylated by Erk1/2 in the BDNF signaling cascade, and the inhibition of this phosphorylation abrogated the BDNF-induced up-regulation of the NR2C and Tiam1 genes. The luciferase reporter assays in combination with mutations of MEK and Etv1 indicated that the Erk-mediated, phosphorylated Etv1 interacted with the Ets motifs of the NR2C promoter sequence and that phosphorylation at both serine 94 and a cluster of threonines and a serine (Thr139, Thr143, and Ser146) of Etv1 was indispensable for the BDNF-mediated activation of the NR2C promoter activity. This study demonstrates that the NR2C and Tiara1 maturation genes are synergistically controlled by the activity-dependent induction of Etv1 and its phosphorylation by the BDNF signaling cascade. activity-dependent regulation | cell culture | cerebellum | protein modification | synaptic maturation doi/10.1073/pnas.1206418109
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titleGene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells.
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0Animals–Pharmacology
1Base Sequence–Cytology
2Brain-Derived Neurotrophic Factor–Metabolism
3Cell Line, Tumor–Genetics
4Cells, Cultured–Metabolism
5Cerebellum–Genetics
6DNA-Binding Proteins–Metabolism
7Extracellular Signal-Regulated MAP Kinases–Drug Effects
8Gene Expression Regulation–Genetics
9Guanine Nucleotide Exchange Factors–Metabolism
10Immunoblotting–Genetics
11Luciferases–Metabolism
12Mice–Drug Effects
13Mice, Inbred Icr–Genetics
14Mutation–Genetics
15Phosphorylation–Metabolism
16Promoter Regions, Genetic–Genetics
17RNA Interference–Metabolism
18Receptor, Trkb–Genetics
19Receptors, N-Methyl-D-Aspartate–Metabolism
20Reverse Transcriptase Polymerase Chain Reaction–Genetics
21Serine–Metabolism
22T-Lymphoma Invasion and Metastasis-Inducing Protein 1–Genetics
23Threonine–Metabolism
24Transcription Factors–Metabolism
25Brain-Derived Neurotrophic Factor
26DNA-Binding Proteins
27Etv1 Protein, Mouse
28Guanine Nucleotide Exchange Factors
29Nr2c Nmda Receptor
30Receptors, N-Methyl-D-Aspartate
31T-Lymphoma Invasion and Metastasis-Inducing Protein 1
32Tiam1 Protein, Mouse
33Transcription Factors
34Threonine
35Serine
36Luciferases
37Receptor, Trkb
38Extracellular Signal-Regulated MAP Kinases
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titleGene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells.
authorAbe, Haruka ; Okazawa, Makoto ; Nakanishi, Shigetada
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1Base Sequence–Cytology
2Brain-Derived Neurotrophic Factor–Metabolism
3Cell Line, Tumor–Genetics
4Cells, Cultured–Metabolism
5Cerebellum–Genetics
6DNA-Binding Proteins–Metabolism
7Extracellular Signal-Regulated MAP Kinases–Drug Effects
8Gene Expression Regulation–Genetics
9Guanine Nucleotide Exchange Factors–Metabolism
10Immunoblotting–Genetics
11Luciferases–Metabolism
12Mice–Drug Effects
13Mice, Inbred Icr–Genetics
14Mutation–Genetics
15Phosphorylation–Metabolism
16Promoter Regions, Genetic–Genetics
17RNA Interference–Metabolism
18Receptor, Trkb–Genetics
19Receptors, N-Methyl-D-Aspartate–Metabolism
20Reverse Transcriptase Polymerase Chain Reaction–Genetics
21Serine–Metabolism
22T-Lymphoma Invasion and Metastasis-Inducing Protein 1–Genetics
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25Brain-Derived Neurotrophic Factor
26DNA-Binding Proteins
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30Receptors, N-Methyl-D-Aspartate
31T-Lymphoma Invasion and Metastasis-Inducing Protein 1
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35Serine
36Luciferases
37Receptor, Trkb
38Extracellular Signal-Regulated MAP Kinases
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