| ○種別 (必須): | □ | 学術論文 (審査論文)
| [継承] |
| ○言語 (必須): | □ | 英語
| [継承] |
| ○招待 (推奨): |
| ○審査 (推奨): | □ | Peer Review
| [継承] |
| ○カテゴリ (推奨): |
| ○共著種別 (推奨): |
| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | 内山 圭司
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 2. | (英) Tomita Mitsuru (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): | □ | ****
| [ユーザ] |
| [継承] |
| 3. | 矢野 雅司 ([徳島大学.技術支援部])
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 4. | 千田 淳司
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 5. | 原 英之
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 6. | (英) Das Rani Nandita (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): | □ | ****
| [ユーザ] |
| [継承] |
| 7. | (英) Nykjaer Anders (日) (読)
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| 8. | 坂口 末廣 ([徳島大学.先端酵素学研究所.基幹研究部門])
| ○役割 (任意): |
| ○貢献度 (任意): |
| ○学籍番号 (推奨): |
| [継承] |
| ○題名 (必須): | □ | (英) Prions amplify through degradation of the VPS10P sorting receptor sortilin. (日)
| [継承] |
| ○副題 (任意): |
| ○要約 (任意): | □ | (英) Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells. (日)
| [継承] |
| ○キーワード (推奨): | 1. | (英) prion (日) (読)
| [継承] |
| 2. | (英) Sortilin (日) (読)
| [継承] |
| 3. | (英) VPS10P (日) (読)
| [継承] |
| ○発行所 (推奨): |
| ○誌名 (必須): | □ | PLoS Pathogens (Public Library of Science)
(pISSN: 1553-7366, eISSN: 1553-7374)
| ○ISSN (任意): | □ | 1553-7374
ISSN: 1553-7366
(pISSN: 1553-7366, eISSN: 1553-7374) Title: PLoS pathogensTitle(ISO): PLoS PathogPublisher: PLOS (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
| [継承] |
| ○巻 (必須): | □ | 13
| [継承] |
| ○号 (必須): | □ | 6
| [継承] |
| ○頁 (必須): | □ | e1006470 e1006470
| [継承] |
| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2017年 6月 30日 (平成 29年 6月 30日)
| [継承] |
| ○URL (任意): |
| ○DOI (任意): | □ | 10.1371/journal.ppat.1006470 (→Scopusで検索)
| [継承] |
| ○PMID (任意): | □ | 28665987 (→Scopusで検索)
| [継承] |
| ○CRID (任意): |
| ○Scopus (任意): |
| ○機関リポジトリ : | □ | 110433
| [継承] |
| ○researchmap (任意): |
| ○評価値 (任意): |
| ○被引用数 (任意): |
| ○指導教員 (推奨): |
| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1371/journal.ppat.1006470 (日)
| [継承] |
| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
| [継承] |