論文 - 詳細
| RRC ID | 53455 |
|---|---|
| 著者 | Alam T, Maruyama H, Li C, Pastuhov SI, Nix P, Bastiani M, Hisamoto N, Matsumoto K. |
| タイトル | Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans. |
| ジャーナル | Nat Commun |
| Abstract |
The molecular mechanisms underlying the ability of axons to regenerate after injury remain poorly understood. Here we show that in Caenorhabditis elegans, axotomy induces ectopic expression of serotonin (5-HT) in axotomized non-serotonergic neurons via HIF-1, a hypoxia-inducible transcription factor, and that 5-HT subsequently promotes axon regeneration by autocrine signalling through the SER-7 5-HT receptor. Furthermore, we identify the rhgf-1 and rga-5 genes, encoding homologues of RhoGEF and RhoGAP, respectively, as regulators of axon regeneration. We demonstrate that one pathway initiated by SER-7 acts upstream of the C. elegans RhoA homolog RHO-1 in neuron regeneration, which functions via G12α and RHGF-1. In this pathway, RHO-1 inhibits diacylglycerol kinase, resulting in an increase in diacylglycerol. SER-7 also promotes axon regeneration by activating the cyclic AMP (cAMP) signalling pathway. Thus, HIF-1-mediated activation of 5-HT signalling promotes axon regeneration by activating both the RhoA and cAMP pathways. |
| 巻・号 | 7 |
| ページ | 10388 |
| 公開日 | 2016-1-21 |
| DOI | 10.1038/ncomms10388 |
| PII | ncomms10388 |
| PMID | 26790951 |
| PMC | PMC4735912 |
| MeSH | Animals Axons / physiology* Axotomy Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclic AMP / metabolism Disease Models, Animal Female Humans Male Nerve Regeneration* Neurodegenerative Diseases / genetics Neurodegenerative Diseases / metabolism* Neurodegenerative Diseases / physiopathology Neurons / metabolism Serotonin / metabolism* Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 12.121 |
| 引用数 | 23 |
| 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 | 7 |
| 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 | tm1325 tm1548 |