ALS の タンパク質 FUS の 液体 から 固体 段階 の 移行 は,病気 の 変異 に よっ て 加速 さ れ て いる
Avinash Patel1, Hyun O Lee1, Louise Jawerth2
1Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Cell
|August 29, 2015
まとめ
FUSのような不規則な領域を持つタンパク質は,機能に不可欠な液体区画を形成しますが,集積傾向があります. これらのコンパートメントの異常な段階の移行は,アミオトロフィック側頭硬化症 (ALS) などの神経変性疾患と関連しています.
科学分野:
- 生物化学
- 分子生物学
- 神経科学
背景:
- 多くのタンパク質は 本質的に不規則な領域を持ち 結合しやすいので 年齢に関連する疾患に寄与します
- アミオトロフィック・サイド・スクレロシス (ALS) に関するFUSタンパク質は,そのような乱れたドメインを含み,プリオンのような特性を表しています.
研究 の 目的:
- FUSタンパク質の生理学的役割を調査する.
- FUS液体コンパートメントの集合状態への移行とそのALS病原性との関連を理解する.
主な方法:
- DNA 損傷部位および細胞質ストレスにおける FUS 局所化を観察する細胞研究.
- 液体 FUS コンパートメントの in vitro 溶解
- 液体から集積物への変換を時間とともにモニターする in vitro 老化実験
主要な成果:
- FUSタンパク質は,特定の条件下 (DNA損傷,ストレス) とin vitroで,細胞内でダイナミックな液体区画を形成する.
- In vitroの老化は,液体のFUS滴が集積状態に変換することを示しています.
- 患者に由来する変異が 液体から集積物への変換を加速します
結論:
- ダイナミックな液体状の区画は,FUSタンパク質の生理学的機能に不可欠です.
- これらのコンパートメントは,機能性と集積リスクの間のトレードオフを提示します.
- FUS液体コンパートメントにおける異常な相変異は,ALSやその他の年齢関連の疾患における重要なメカニズムとして提案されています.
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