マンネン タロウ
萬年 太郎
MANNEN TARO
所属 生命科学部 生命医科学科
職名 助教
言語種別 英語
発行・発表の年月 2021/09
形態種別 研究論文(学術雑誌)
査読 査読あり
標題 C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers.
執筆形態 共著
掲載誌名 Nature communications
掲載区分 国外
巻・号・頁 12(1),5301
著者・共著者 Nanaura Hitoki, Kawamukai Honoka, Fujiwara Ayano, Uehara Takeru, Aiba Yuichiro, Nakanishi Mari, Shiota Tomo, Hibino Masaki, Wiriyasermkul Pattama, Kikuchi Sotaro, Nagata Riko, Matsubayashi Masaya, Shinkai Yoichi, Niwa Tatsuya, Mannen Taro, Morikawa Naritaka, Iguchi Naohiko, Kiriyama Takao, Morishima Ken, Inoue Rintaro, Sugiyama Masaaki, Oda Takashi, Kodera Noriyuki, Toma-Fukai Sachiko, Sato Mamoru, Taguchi Hideki, Nagamori Shushi, Shoji Osami, Ishimori Koichiro, Matsumura Hiroyoshi, Sugie Kazuma
概要 Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration.
DOI 10.1038/s41467-021-25560-0
ISSNコード 2041-1723
PMID 34489423