論文 - 詳細
| RRC ID | 34860 |
|---|---|
| 著者 | Abe H, Okazawa M, Nakanishi S. |
| タイトル | Gene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
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(+) channels, and voltage-dependent Ca(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 Tiam1 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 Tiam1 maturation genes are synergistically controlled by the activity-dependent induction of Etv1 and its phosphorylation by the BDNF signaling cascade. |
| 巻・号 | 109(22) |
| ページ | 8734-9 |
| 公開日 | 2012-5-29 |
| DOI | 10.1073/pnas.1206418109 |
| PII | 1206418109 |
| PMID | 22586091 |
| PMC | PMC3365191 |
| MeSH | Animals Base Sequence Brain-Derived Neurotrophic Factor / pharmacology* Cell Line, Tumor Cells, Cultured Cerebellum / cytology Cerebellum / metabolism* DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Regulation / drug effects* Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism Immunoblotting Luciferases / genetics Luciferases / metabolism Mice Mice, Inbred ICR Mutation Phosphorylation / drug effects Promoter Regions, Genetic / genetics RNA Interference Receptor, trkB / genetics Receptor, trkB / metabolism Receptors, N-Methyl-D-Aspartate / genetics Receptors, N-Methyl-D-Aspartate / metabolism Reverse Transcriptase Polymerase Chain Reaction Serine / genetics Serine / metabolism T-Lymphoma Invasion and Metastasis-inducing Protein 1 Threonine / genetics Threonine / metabolism Transcription Factors / genetics* Transcription Factors / metabolism |
| IF | 9.412 |
| 引用数 | 14 |
| WOS 分野 | NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-Flag-Etv1 (RDB13214) pCAG-Flag-Etv1act (RDB13215). |