2018年8月24日
Characterization of membrane penetration and cytotoxicity of C9orf72-encoding arginine-rich dipeptides
SCIENTIFIC REPORTS
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- 巻
- 8
- 号
- 1
- 開始ページ
- 12740
- 終了ページ
- 12740
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41598-018-31096-z
- 出版者・発行元
- NATURE PUBLISHING GROUP
Cell-penetrating peptides (CPPs) including arginine-rich peptides are attracting a lot of attention due to their potential as a novel intracellular drug delivery tool without substantial toxicity. On the other hand, disease-associated arginine-rich CPPs, such as poly-PR and poly-GR translated from C9orf72 gene, also efficiently enter neuronal cells and then kill them. Although both non-harmful CPPs and harmful poly-PR/GR penetrate the plasma membrane using same arginine residues, little is known about the factors which determine the toxicity of the pathogenic CPPs. Here, we show that poly-PR and poly-GR, but not other Arg-rich CPPs, specifically distributed to nucleolus via interaction with RNA. Importantly, C9orf72-dipeptides, but not other Arg-rich CPPs, caused inhibition of protein translation and cell death. Raising extracellular pH enhanced the cell penetration of poly-PR. The repeat number of (PR) affected the secondary structure and determined the intracellular delivery rate and neurotoxicity, and enforced intracellular delivery of non-penetrating short poly-PR peptide caused cell death, suggesting that modulation of extracellular environment to inhibit the uptake of Arg-ric
- リンク情報
- ID情報
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- DOI : 10.1038/s41598-018-31096-z
- ISSN : 2045-2322
- PubMed ID : 30143685
- PubMed Central 記事ID : PMC6109075