Egr4 mediates BDNF induction of KCC2 transcription

Anastasia Ludwig, Pavel Uvarov, Shetal Soni, Judith Thomas-Crusells, Matti S Airaksinen, Claudio Rivera

Research output: Contribution to journalArticleScientificpeer-review

Abstract

A major event in the maturation of CNS GABAergic transmission is the qualitative change in GABAA mediated responses from depolarizing to hyperpolarizing. In cortical regions this is attributed to the increased expression of KCC2b, the main isoform of the neuron specific K-Cl cotransporter KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate the KCC2b promoter. Here we demonstrate that in immature hippocampal neurons BDNF robustly induces ERK1/2- dependent Egr4 expression and rapid Egr4- dependent activation of the KCC2b promoter. The subsequent increase in KCC2b mRNA contributes to the expression of total KCC2 protein levels. These results indicate that Egr4 is an important component in the mechanism of BDNF-dependent KCC2 gene regulation via the ERK1/2 pathway in immature neurons.
Original languageEnglish
JournalJournal of Neuroscience
Volume31
Issue number2
Pages (from-to)644-649
Number of pages6
ISSN0270-6474
DOIs
Publication statusPublished - 12 Jan 2011
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 311 Basic medicine
  • epilepsy
  • 1182 Biochemistry, cell and molecular biology
  • synaptic inhibition
  • neurotrophic factor
  • 1183 Plant biology, microbiology, virology
  • 1184 Genetics, developmental biology, physiology

Cite this

Ludwig, Anastasia ; Uvarov, Pavel ; Soni, Shetal ; Thomas-Crusells, Judith ; Airaksinen, Matti S ; Rivera, Claudio. / Egr4 mediates BDNF induction of KCC2 transcription. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 2. pp. 644-649.
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title = "Egr4 mediates BDNF induction of KCC2 transcription",
abstract = "A major event in the maturation of CNS GABAergic transmission is the qualitative change in GABAA mediated responses from depolarizing to hyperpolarizing. In cortical regions this is attributed to the increased expression of KCC2b, the main isoform of the neuron specific K-Cl cotransporter KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate the KCC2b promoter. Here we demonstrate that in immature hippocampal neurons BDNF robustly induces ERK1/2- dependent Egr4 expression and rapid Egr4- dependent activation of the KCC2b promoter. The subsequent increase in KCC2b mRNA contributes to the expression of total KCC2 protein levels. These results indicate that Egr4 is an important component in the mechanism of BDNF-dependent KCC2 gene regulation via the ERK1/2 pathway in immature neurons.",
keywords = "311 Basic medicine, epilepsy, 1182 Biochemistry, cell and molecular biology, synaptic inhibition, neurotrophic factor, 1183 Plant biology, microbiology, virology, 1184 Genetics, developmental biology, physiology",
author = "Anastasia Ludwig and Pavel Uvarov and Shetal Soni and Judith Thomas-Crusells and Airaksinen, {Matti S} and Claudio Rivera",
year = "2011",
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doi = "10.1523/JNEUROSCI.2006-10.2011",
language = "English",
volume = "31",
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Egr4 mediates BDNF induction of KCC2 transcription. / Ludwig, Anastasia; Uvarov, Pavel; Soni, Shetal; Thomas-Crusells, Judith; Airaksinen, Matti S; Rivera, Claudio.

In: Journal of Neuroscience, Vol. 31, No. 2, 12.01.2011, p. 644-649.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Egr4 mediates BDNF induction of KCC2 transcription

AU - Ludwig, Anastasia

AU - Uvarov, Pavel

AU - Soni, Shetal

AU - Thomas-Crusells, Judith

AU - Airaksinen, Matti S

AU - Rivera, Claudio

PY - 2011/1/12

Y1 - 2011/1/12

N2 - A major event in the maturation of CNS GABAergic transmission is the qualitative change in GABAA mediated responses from depolarizing to hyperpolarizing. In cortical regions this is attributed to the increased expression of KCC2b, the main isoform of the neuron specific K-Cl cotransporter KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate the KCC2b promoter. Here we demonstrate that in immature hippocampal neurons BDNF robustly induces ERK1/2- dependent Egr4 expression and rapid Egr4- dependent activation of the KCC2b promoter. The subsequent increase in KCC2b mRNA contributes to the expression of total KCC2 protein levels. These results indicate that Egr4 is an important component in the mechanism of BDNF-dependent KCC2 gene regulation via the ERK1/2 pathway in immature neurons.

AB - A major event in the maturation of CNS GABAergic transmission is the qualitative change in GABAA mediated responses from depolarizing to hyperpolarizing. In cortical regions this is attributed to the increased expression of KCC2b, the main isoform of the neuron specific K-Cl cotransporter KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate the KCC2b promoter. Here we demonstrate that in immature hippocampal neurons BDNF robustly induces ERK1/2- dependent Egr4 expression and rapid Egr4- dependent activation of the KCC2b promoter. The subsequent increase in KCC2b mRNA contributes to the expression of total KCC2 protein levels. These results indicate that Egr4 is an important component in the mechanism of BDNF-dependent KCC2 gene regulation via the ERK1/2 pathway in immature neurons.

KW - 311 Basic medicine

KW - epilepsy

KW - 1182 Biochemistry, cell and molecular biology

KW - synaptic inhibition

KW - neurotrophic factor

KW - 1183 Plant biology, microbiology, virology

KW - 1184 Genetics, developmental biology, physiology

U2 - 10.1523/JNEUROSCI.2006-10.2011

DO - 10.1523/JNEUROSCI.2006-10.2011

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