論文 - 詳細
| RRC ID | 83801 |
|---|---|
| 著者 | Gao Y, Tan YS, Lin J, Chew LY, Aung HY, Palliyana B, Gujar MR, Lin KY, Kondo S, Wang H. |
| タイトル | SUMOylation of Warts kinase promotes neural stem cell reactivation. |
| ジャーナル | Nat Commun |
| Abstract |
A delicate balance between neural stem cell (NSC) quiescence and proliferation is important for adult neurogenesis and homeostasis. Small ubiquitin-related modifier (SUMO)-dependent post-translational modifications cause rapid and reversible changes in protein functions. However, the role of the SUMO pathway during NSC reactivation and brain development is not established. Here, we show that the key components of the SUMO pathway play an important role in NSC reactivation and brain development in Drosophila. Depletion of SUMO/Smt3 or SUMO conjugating enzyme Ubc9 results in notable defects in NSC reactivation and brain development, while their overexpression leads to premature NSC reactivation. Smt3 protein levels increase with NSC reactivation, which is promoted by the Ser/Thr kinase Akt. Warts/Lats, the core protein kinase of the Hippo pathway, can undergo SUMO- and Ubc9-dependent SUMOylation at Lys766. This modification attenuates Wts phosphorylation by Hippo, leading to the inhibition of the Hippo pathway, and consequently, initiation of NSC reactivation. Moreover, inhibiting Hippo pathway effectively restores the NSC reactivation defects induced by SUMO pathway inhibition. Overall, our study uncovered an important role for the SUMO-Hippo pathway during Drosophila NSC reactivation and brain development. |
| 巻・号 | 15(1) |
| ページ | 8557 |
| 公開日 | 2024-10-17 |
| DOI | 10.1038/s41467-024-52569-y |
| PII | 10.1038/s41467-024-52569-y |
| PMID | 39419973 |
| PMC | PMC11487185 |
| MeSH | Animals Brain / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Neural Stem Cells* / metabolism Neurogenesis Phosphorylation Protein Kinases Protein Serine-Threonine Kinases* / genetics Protein Serine-Threonine Kinases* / metabolism Proto-Oncogene Proteins c-akt / metabolism Signal Transduction* Small Ubiquitin-Related Modifier Proteins / genetics Small Ubiquitin-Related Modifier Proteins / metabolism Sumoylation* Ubiquitin-Conjugating Enzyme UBC9 Ubiquitin-Conjugating Enzymes* / genetics Ubiquitin-Conjugating Enzymes* / metabolism |
| IF | 12.121 |
| 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 | 27 |
| 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 | |
| ショウジョウバエ | HMS00067 |