Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos

Jianxin Bao, Hana Lin, Yannan Ouyang, Debin Lei, Abdullah Osman, Tae Wan Kim, Lin Mei, Penggao Dai, Kevin K. Ohlemiller, Richard T. Ambron

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Neuregulin-1 (Nrg-1) contains an intracellular domain (Nrg-ICD) that translocates into the nucleus, where it may regulate gene expression upon neuronal depolarization. However, the identity of its target promoters and the mechanisms by which it regulates transcription have been elusive. Here we report that, in the mouse cochlea, synaptic activity increases the level of nuclear Nrg-ICD and upregulates postsynaptic density protein-95 (PSD-95), a scaffolding protein that is enriched in post-synaptic structures. Nrg-ICD enhances the transcriptional activity of the PSD-95 promoter by binding to a zinc-finger transcription factor, Eos. The Nrg-ICD-Eos complex induces endogenous PSD-95 expression in vivo through a signaling pathway that is mostly independent of γ-secretase regulation. This upregulation of PSD-95 expression by the Nrg-ICD-Eos complex provides a molecular basis for activity-dependent synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)1250-1258
Number of pages9
JournalNature Neuroscience
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2004

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Neuregulin-1
Up-Regulation
Amyloid Precursor Protein Secretases
Neuronal Plasticity
Cochlea
Zinc Fingers
Transcription Factors
Gene Expression
postsynaptic density proteins
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bao, J., Lin, H., Ouyang, Y., Lei, D., Osman, A., Kim, T. W., ... Ambron, R. T. (2004). Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nature Neuroscience, 7(11), 1250-1258. https://doi.org/10.1038/nn1342

Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. / Bao, Jianxin; Lin, Hana; Ouyang, Yannan; Lei, Debin; Osman, Abdullah; Kim, Tae Wan; Mei, Lin; Dai, Penggao; Ohlemiller, Kevin K.; Ambron, Richard T.

In: Nature Neuroscience, Vol. 7, No. 11, 01.11.2004, p. 1250-1258.

Research output: Contribution to journalArticle

Bao, J, Lin, H, Ouyang, Y, Lei, D, Osman, A, Kim, TW, Mei, L, Dai, P, Ohlemiller, KK & Ambron, RT 2004, 'Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos', Nature Neuroscience, vol. 7, no. 11, pp. 1250-1258. https://doi.org/10.1038/nn1342
Bao J, Lin H, Ouyang Y, Lei D, Osman A, Kim TW et al. Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nature Neuroscience. 2004 Nov 1;7(11):1250-1258. https://doi.org/10.1038/nn1342
Bao, Jianxin ; Lin, Hana ; Ouyang, Yannan ; Lei, Debin ; Osman, Abdullah ; Kim, Tae Wan ; Mei, Lin ; Dai, Penggao ; Ohlemiller, Kevin K. ; Ambron, Richard T. / Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. In: Nature Neuroscience. 2004 ; Vol. 7, No. 11. pp. 1250-1258.
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