演題詳細
Poster
ポリグルタミン病、ALS、脊髄小脳変性症、その他の神経変性疾患
Polyglutamine Diseases, ALS, SCD, Other Neurodegenerative Disorder
開催日 | 2014/9/11 |
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時間 | 11:00 - 12:00 |
会場 | Poster / Exhibition(Event Hall B) |
メチル化阻害薬の家族性ALS関連FUS/TLS変異体の細胞内局在への影響
The effect of methylation inhibitor on the cytoplasmic mislocalization of ALS-linked FUS/TLS mutant
- P1-309
- 山口 淳 / Atsushi Yamaguchi:1 高梨 啓介 / Keisuke Takanashi:1 北城 敬子 / Keiko Kitajo:1
- 1:千葉大学 / Dept. of Neurobiology, Graduate School of Medicine, Chiba University
FUS/TLS, one of causative gene for familial ALS (fALS), encodes a multifunctional DNA/RNA binding protein. FUS/TLS, continuously nucleo-cytoplasmic shuttling, contains an N-terminal QGSY (Gln-Gly-Ser-Tyr)-rich region, a Glycine-rich region, an RRM (RNA recognition motif), two RGG (Arg-Gly-Gly ) repeats divided by a zinc finger motif, and a highly conserved C-terminal non-classical NLS (nuclear localization signal) recognized by nuclear transporter transportin. A variety of fALS-linked mutations are clustered in the C-terminal NLS, which impairs the interaction between NLS and import receptor transportin resulting in the cytoplasmic mislocalization. Since arginine methylation is implicated in the subcellular localization of FUS/TLS, we examined the effect of methylation inhibitors on the subcellular localization of ALS-linked mutant FUS P525L. The treatment with global methylation inhibitor AdOx (adenosine dialdehyde) remarkably reuduced the cytosoplasmic mislocalization of FUS/TLS. The pull down assay demonstrated the binding of FUS/TLS with transprotin was potentiated by the treatment with AdOx. The deletion of RGG domains abolished the effect of AdOx, which suggests the arginine methylation in RGG domains might be essential for AdOx treatment to modulate the binding to transportin.