Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons

Fei Zheng; Xianju Zhou; Yongneng Luo; Hua Xiao; Gary Wayman; Hongbing Wang

doi:10.1371/journal.pone.0028441

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Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons

Journal article

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Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons

Fei Zheng, Xianju Zhou, Yongneng Luo, Hua Xiao, Gary Wayman and Hongbing Wang

PloS one, Vol.6(12), pp.e28441-e28441

2011

DOI: https://doi.org/10.1371/journal.pone.0028441

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https://hdl.handle.net/2376/103357

PMCID: PMC3235121

PMID: 22174809

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Abstract

Protein Kinases - metabolism

Brain-Derived Neurotrophic Factor - genetics

Transcription, Genetic - drug effects

Calcium - pharmacology

Luciferases - metabolism

Calcium Channels - metabolism

RNA, Messenger - genetics

Receptors, N-Methyl-D-Aspartate - metabolism

Rats

Exons - genetics

Signal Transduction - genetics

RNA, Messenger - metabolism

Cerebral Cortex - cytology

Rats, Sprague-Dawley

N-Methylaspartate - pharmacology

Gene Expression Regulation - drug effects

Animals

Signal Transduction - drug effects

Models, Biological

Potassium Chloride - pharmacology

Cyclic AMP Response Element-Binding Protein - metabolism

Neurons - metabolism

Response Elements - genetics

Neurons - drug effects

Activity-dependent transcription of brain-derived neurotrophic factor (BDNF) has been studied as an important model to elucidate the mechanisms underlying numerous aspects of neuroplasticity. It has been extensively emphasized that Ca(2+) influx through different routes may have significantly different effects on BDNF transcription. Here, we examined the regulatory property of the major calcium responsive elements (CaRE) in BDNF promoter IV in cultured rat cortical neurons. BDNF promoter IV, as well as CaRE1 and CaRE3, was significantly activated by Ca(2+) influx through L-type voltage-gated calcium channel (L-VGCC) or NMDA receptor (NMDAR). However, the L-VGCC- and NMDAR-mediated activation of CaRE was differentially regulated by different Ca(2+)-stimulated protein kinases. Specifically, PKA, CaMKI, and CaMKIV activity were required for L-VGCC-, but not NMDAR-mediated CaRE1 activation. CaMKI activity was required for NMDAR- but not L-VGCC-mediated CaRE3 activation. Surprisingly, the activation of CaRF, a previously identified transcription factor for CaRE1, was stimulated via L-VGCC but not NMDAR, and required MEK, PI3K and CaMKII activity. These results suggest a new working model that activity-dependent BDNF IV up-regulation may be coordinately mediated by CaRE1 and CaRE3 activity, which show different responses to Ca(2+)-stimulated kinases. Our data also explain how the individual cis-element in BDNF promoter is distinctively coupled to different Ca(2+) routes.

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Title: Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons
Creators: Fei Zheng - Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America
Xianju Zhou
Yongneng Luo
Hua Xiao
Gary Wayman
Hongbing Wang
Publication Details: PloS one, Vol.6(12), pp.e28441-e28441
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: MH086032 / NIMH NIH HHS R01 DK066110 / NIDDK NIH HHS R01 MH076906 / NIMH NIH HHS R01 MH086032 / NIMH NIH HHS MH076906 / NIMH NIH HHS DK066110 / NIDDK NIH HHS
Identifiers: 99900546798101842
Language: English
Resource Type: Journal article