書誌事項
- タイトル別名
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- Differential toxicity and localization of arginine-rich C9ORF72 dipeptide repeat proteins depend on de-clustering of positive charges
抄録
<p>Recently, many Amyotrophic lateral sclerosis (ALS)-causing proteins reportedly undergo liquid-liquid phase separation (LLPS). It has also been shown that arginine-rich dipeptide repeat proteins (R-DPRs), poly(PR) and poly(GR), expressed from mutant C9ORF72 are prone to phase separation, and associate with membrane-less organelles formed by LLPS, disturbing their functions. Although R-DPRs share many biochemical features, such as the alternating of Arg, their subcellular localization and toxicity mechanisms are different. However, the mechanisms underlying these differences are unknown. In this study, we analyzed localization, intermolecular interactions, and LLPS of R-DPR variants, and found that these differences are determined by the degree of segregation of Arg charges (Miyagi et al., iScience 2023). In poly(PR), the segregation of arginine side chains by Pro is a critical factor in promoting nucleolar incorporation. In addition, Pro allowed interactions with molecules in a weak but highly multivalent manner. Still, Gly was incapable of separating the Arg well, so poly(GR) showed static localization in the cytosol. Poly(GR) binds to molecules in a strong, but less multivalent manner than poly(PR). These data reveal critical factors that determine biochemical differences in the R-DPRs.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 97 (0), 3-B-SS14-1-, 2023
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390298742739169664
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- ISSN
- 24354953
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
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- 抄録ライセンスフラグ
- 使用不可