Kobe University · Graduate School of Medicine / Faculty of Medicine

Research keywordsタニサイト・視床下部・Cell・biology・Axon・Signal・transduction

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• Identification of Sox2 and NeuN Double-Positive Cells in the Mouse Hypothalamic Arcuate Nucleus and Their Reduction in Number With Aging2021 · 2021年03月, FRONTIERS IN AGING NEUROSCIENCE, 12, 英語
• Heavy Metal Stress Assay of Caenorhabditis elegans2017 · 2017年06月, BIO-PROTOCOL, 7(11) (11), 英語
• Chemical Signaling Regulates Axon Regeneration via the GPCR-Gqα Pathway in Caenorhabditis elegans.Chemical communication controls a wide range of behaviors via conserved signaling networks. Axon regeneration in response to injury is determined by the interaction between the extracellular environment and intrinsic growth potential. In this study, we investigated the role of chemical signaling in axon regeneration in Caenorhabditis elegans We find that the enzymes involved in ascaroside pheromone biosynthesis, ACOX-1.1, ACOX-1.2, and DAF-22, participate in axon regeneration by producing a dauer-inducing ascaroside, ascr#5. We demonstrate that the chemoreceptor genes, srg-36 and srg-37, which encode G-protein-coupled receptors for ascr#5, are required for adult-specific axon regeneration. Furthermore, the activating mutation in egl-30 encoding Gqα suppresses axon regeneration defective phenotype in acox-1.1 and srg-36 srg-37 mutants. Therefore, the ascaroside signaling system provides a unique example of a signaling molecule that regulates the regenerative pathway in the nervous system.SIGNIFICANCE STATEMENT In Caenorhabditis elegans, axon regeneration is positively regulated by the EGL-30 Gqα-JNK MAP kinase cascade. However, it remains unclear what signals activate the EGL-30 pathway in axon regeneration. Here, we show that SRG-36 and SRG-37 act as upstream G-protein-coupled receptors (GPCRs) that activate EGL-30. C. elegans secretes a family of small-molecule pheromones called ascarosides, which serve various functions in chemical signaling. SRG-36 and SRG-37 are GPCRs for the dauer-inducing ascaroside ascr#5. Consistent with this, we found that ascr#5 activates the axon regeneration pathway via SRG-36/SRG-37 and EGL-30. Thus, ascaroside signaling promotes axon regeneration by activating the GPCR-Gqα pathway.
• Caenorhabditis elegans F-box protein promotes axon regeneration by inducing degradation of the Mad transcription factor.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 C. 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.

• 個体老化における視床下部タニサイトのネクチン-1の機能と作用機構 清水 達太 国立研究開発法人日本医療研究開発機構, 革新的先端研究開発支援事業 (AMED-PRIME), 2023年10月 - 2027年03月, 研究代表者2023 · KUID parsed section
• α2タニサイトの構造・機能とネクチン１の発現 清水 達太 日本学術振興会, 科学研究費助成事業, 研究活動スタート支援, 神戸大学, 2020年09月11日 - 2022年03月31日 様々な生物の寿命は食事制限により延長するが、個体の老化と寿命を制御する機構の大部分は未解明である。視床下部の第三脳室の側壁を覆うタニサイトは脳脊髄液中のグルコース濃度を感知するほか、成体でも神経幹/前駆細胞機能を持つ。近年、タニサイトが個体の寿命延長に関与することが示唆されているが、加齢時の神経幹/前駆細胞機能の維持機構は不明である。本研究では、神経幹細胞機能の高いタニサイトで特異的に発現する細胞接着分子ネクチンを同定し、神経幹細胞機能の維持に関与する可能性を見出した。また、摂食行動を制御する弓状核に幹細胞マーカーSox2陽性の神経細胞の存在を見出し、加齢により細胞数が減少することを報告した。2020 · KUID parsed section
• 視床下部タニサイトにおけるネクチン-1によるグルコース濃度の感知制御機構
• α2タニサイトの構造・機能とネクチン１の発現

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