論文 - 詳細
| RRC ID | 65385 |
|---|---|
| 著者 | Shimizu T, Pastuhov SI, Hanafusa H, Sakai Y, Todoroki Y, Hisamoto N, Matsumoto K. |
| タイトル | Caenorhabditis elegans F-Box Protein Promotes Axon Regeneration by Inducing Degradation of the Mad Transcription Factor. |
| ジャーナル | J Neurosci |
| Abstract |
In Caenorhabditis elegans, axon regeneration is activated by a signaling cascade through the receptor tyrosine kinase (RTK) SVH-2. Axonal injury induces svh-2 gene expression by degradation of the Mad-like transcription factor MDL-1. In this study, we identify the svh-24/sdz-33 gene encoding a protein containing F-box and F-box-associated domains as a regulator of axon regeneration in motor neurons. We find that sdz-33 is required for axon injury-induced svh-2 expression. SDZ-33 targets MDL-1 for poly-ubiquitylation and degradation. Furthermore, we demonstrate that SDZ-33 promotes axotomy-induced nuclear degradation of MDL-1, resulting in the activation of svh-2 expression in animals. These results suggest that the F-box protein is required for RTK signaling in the control of axon regeneration.SIGNIFICANCE STATEMENT In Caenorhabditis elegans, axon regeneration is positively regulated by the growth factor SVH-1 and its receptor tyrosine kinase SVH-2. Expression of the svh-2 gene is induced by axonal injury via the Ets-like transcription factor ETS-4, whose transcriptional activity is inhibited by the Mad-like transcription factor MDL-1. Axon injury leads to the degradation of MDL-1, and this is linked to the activation of ETS-4 transcriptional activity. In this study, we identify the sdz-33 gene encoding a protein containing an F-box domain as a regulator of axon regeneration. We demonstrate that MDL-1 is poly-ubiquitylated and degraded through the SDZ-33-mediated 26S proteasome pathway. These results reveal that an F-box protein promotes axon regeneration by degrading the Mad transcription factor. |
| 巻・号 | 41(11) |
| ページ | 2373-2381 |
| 公開日 | 2021-3-17 |
| DOI | 10.1523/JNEUROSCI.1024-20.2021 |
| PII | JNEUROSCI.1024-20.2021 |
| PMID | 33514673 |
| PMC | PMC7984584 |
| MeSH | Amino Acids / metabolism Animals Animals, Genetically Modified Axons / physiology Axotomy Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology* F-Box Proteins / genetics F-Box Proteins / physiology* Motor Neurons / physiology Nerve Regeneration / genetics Nerve Regeneration / physiology* Plasmids Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism Receptor Protein-Tyrosine Kinases / physiology Ubiquitin |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| 線虫 | tm737 tm1210 tm311 |