論文 - 詳細
| RRC ID | 81409 |
|---|---|
| 著者 | Matsuno H, Tsuchimine S, Fukuzato N, O'Hashi K, Kunugi H, Sohya K. |
| タイトル | Sirtuin 6 is a regulator of dendrite morphogenesis in rat hippocampal neurons. |
| ジャーナル | Neurochem Int |
| Abstract |
Sirtuin 6 (SIRT6), a member of the Sirtuin family, acts as nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase, mono-adenosine diphosphate (ADP)-ribosyltransferase, and fatty acid deacylase, and plays critical roles in inflammation, aging, glycolysis, and DNA repair. Accumulating evidence has suggested that SIRT6 is involved in brain functions such as neuronal differentiation, neurogenesis, and learning and memory. However, the precise molecular roles of SIRT6 during neuronal circuit formation are not yet well understood. In this study, we tried to elucidate molecular roles of SIRT6 on neurite development by using primary-cultured hippocampal neurons. We observed that SIRT6 was abundantly localized in the nucleus, and its expression was markedly increased during neurite outgrowth and synaptogenesis. By using shRNA-mediated SIRT6-knockdown, we show that both dendritic length and the number of dendrite branches were significantly reduced in the SIRT6-knockdown neurons. Microarray and subsequent gene ontology analysis revealed that reducing SIRT6 caused the downregulation of immediate early genes (IEGs) and alteration of several biological processes including MAPK (ERK1/2) signaling. We found that nuclear accumulation of phosphorylated ERK1/2 was significantly reduced in SIRT6-knockdown neurons. Overexpression of SIRT6 promoted dendritic length and branching, but the mutants lacking deacetylase activity had no significant effect on the dendritic morphology. Collectively, the presented findings reveal a role of SIRT6 in dendrite morphogenesis, and suggest that SIRT6 may act as an important regulator of ERK1/2 signaling pathway that mediates IEG expression, which leads to dendritic development. |
| 巻・号 | 145 |
| ページ | 104959 |
| 公開日 | 2021-5-1 |
| DOI | 10.1016/j.neuint.2021.104959 |
| PII | S0197-0186(21)00005-X |
| PMID | 33444676 |
| MeSH | Animals Animals, Newborn Cells, Cultured Dendrites / metabolism* Gene Knockdown Techniques / methods Hippocampus / cytology* Hippocampus / metabolism* Neurogenesis / physiology* Neurons / metabolism* Rats Sirtuins / biosynthesis* Sirtuins / deficiency Sirtuins / genetics |
| IF | 3.881 |
| 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-HIVgp (RDB04394) |