論文 - 詳細
| RRC ID | 81368 |
|---|---|
| 著者 | Tanaka T, Yano T, Usuki S, Seo Y, Mizuta K, Okaguchi M, Yamaguchi M, Hanyu-Nakamura K, Toyama-Sorimachi N, Brückner K, Nakamura A. |
| タイトル | Endocytosed dsRNAs induce lysosomal membrane permeabilization that allows cytosolic dsRNA translocation for Drosophila RNAi responses. |
| ジャーナル | Nat Commun |
| Abstract |
RNA interference (RNAi) is a gene-silencing mechanism triggered by the cytosolic entry of double-stranded RNAs (dsRNAs). Many animal cells internalize extracellular dsRNAs via endocytosis for RNAi induction. However, it is not clear how the endocytosed dsRNAs are translocated into the cytosol across the endo/lysosomal membrane. Herein, we show that in Drosophila S2 cells, endocytosed dsRNAs induce lysosomal membrane permeabilization (LMP) that allows cytosolic dsRNA translocation. LMP mediated by dsRNAs requires the lysosomal Cl-/H+ antiporter ClC-b/DmOstm1. In clc-b or dmostm1 knockout S2 cells, extracellular dsRNAs are endocytosed and reach the lysosomes normally but fail to enter the cytosol. Pharmacological induction of LMP restores extracellular dsRNA-directed RNAi in clc-b or dmostm1-knockout cells. Furthermore, clc-b or dmostm1 mutant flies are defective in extracellular dsRNA-directed RNAi and its associated antiviral immunity. Therefore, endocytosed dsRNAs have an intrinsic ability to induce ClC-b/DmOstm1-dependent LMP that allows cytosolic dsRNA translocation for RNAi responses in Drosophila cells. |
| 巻・号 | 15(1) |
| ページ | 6993 |
| 公開日 | 2024-8-14 |
| DOI | 10.1038/s41467-024-51343-4 |
| PII | 10.1038/s41467-024-51343-4 |
| PMID | 39143098 |
| PMC | PMC11324899 |
| MeSH | Animals Cell Line Chloride Channels / genetics Chloride Channels / metabolism Cytosol* / metabolism Drosophila / genetics Drosophila / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Endocytosis* Intracellular Membranes / metabolism Lysosomes* / metabolism Permeability RNA Interference* RNA, Double-Stranded* / 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 | 22 |
| 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 | DGRC#119050 DGRC#119051 DGRC#119052 DGRC#119053 |