生物のプロテオスタシスの調節は,トランス細胞チャペロンによるシグナル伝達によって行われる
Patricija van Oosten-Hawle1, Robert S Porter, Richard I Morimoto
1Department Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Cell
|June 11, 2013
まとめ
生物は,全身的なストレス反応を通して,タンパク質の健康を維持します. 1つの組織における熱ショックタンパク質90 (HSP90) の強化は,他の組織を保護し,細胞間監視システムを明らかにすることができます.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- メタゾア類は,多様な組織特異のタンパク質にもかかわらず,生物のプロテオスタシスを維持するという課題に直面しています.
- タンパク質が誤った折り畳みから生じるタンパク質毒性ストレスが,細胞と生物の健康を脅かします.
- チャペロンは,熱ショックタンパク質90 (HSP90) のように,適切なタンパク質の折り畳みに不可欠です.
研究 の 目的:
- メタゾアにおける全身性プロテオスタシスのメカニズムを調査する.
- 局所的なタンパク質の誤折れが全身のストレス反応を誘発できるかどうかを判断する.
- プロテオスタシスの維持におけるHSP90と細胞間通信の役割を明らかにする.
主な方法:
- タンパク質の折りたたみとストレス反応を研究するためのモデル生物としてC. elegansを使用した.
- タンパク質毒性ストレスを模倣するために,筋肉細胞の転移性タンパク質の誘発表現.
- 異なる組織 (筋肉,腸,ニューロン) のHSP90発現を操作した.
- HSP90の発現を調節するPHA-4転写因子の役割を調査した.
主要な成果:
- 筋肉細胞における転移性タンパク質の発現は,複数の組織にわたる全身的ストレス反応を誘発する.
- 筋肉,腸,または神経細胞における強化されたHSP90発現は,筋肉におけるタンパク質の誤折れを効果的に抑制しました.
- このHSP90の細胞非自律的制御は,PHA-4転写因子によって調節される転写フィードバックによって媒介されます.
- 生物のプロテオスタシスに不可欠なトランス細胞チャペロン信号伝達経路が実証されました.
結論:
- 局所的なタンパク質の誤折れは,全身的,細胞非自律的なチャペロン反応を誘発する可能性があります.
- PHA-4によって調節される組織間通信は,生物のプロテオスタシスの維持に不可欠です.
- この細胞間信号伝達は,生物のストレス感知監視の基礎となる.
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