核は,相分離したタンパク質の品質管理コンパートメントとして機能する

F Frottin¹, F Schueder^2,3, S Tiwary⁴

¹Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.

Science (New York, N.Y.)

|July 13, 2019

まとめ

核細胞はストレスバッファとして作用し,誤った核タンパク質を一時的に保存し,結合を防止します. このシェーパーロンのような機能は逆転可能ですが,長時間ストレス下では機能しなくなり,タンパク質の品質管理が損なわれます.

科学分野:

細胞生物学
分子生物学
生物化学

背景:

核プロテオームには多くのストレスに敏感なタンパク質が含まれており堅固な品質管理メカニズムが必要です
タンパク質の構造維持は,特にストレス下では,細胞機能に不可欠です.

研究の目的:

ストレス下での核タンパク質の品質管理における核細胞の役割を調査する.
核が誤った折りたたまれたタンパク質を処理するメカニズムを解明する.

主な方法:

ストレスを受けた哺乳類の組織培養細胞を使用した.
顕微鏡を用いて核内の誤った折りたたみのタンパク質の振る舞いを観察した.
核タンパク質 (例えばNPM1) と熱ショックタンパク質70 (Hsp70) のタンパク質管理への関与を評価した.

主要な成果:

誤った折りたたみタンパク質は,ストレス下にある核細胞の粒状成分 (GC) 段階に蓄積される.
NPM1のような核タンパク質は一時的に誤折れタンパク質に結合し,その移動性を低下させ,結合を防ぐ.
Hsp70は,ストレス回復時に核からタンパク質の再折りと除去を媒介した.
長期にわたるストレスにより,核子マトリックスが液体状から固体状に変化し,不可逆的な集積と品質管理の失敗を引き起こした.

結論:

核細胞はストレス中に核タンパク質の維持を助けるシェーパーロンのような性質を示します
核は誤った折り畳みのタンパク質のダイナミックな貯蔵場所として機能し容量は限られています
長期にわたるストレス下での核機能障害はタンパク質の品質管理メカニズムの重要なバランスを強調しています

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