ER-ミトコンドリアのインターフェースのシグマ-1受容体チャペロンは,Ca2+) 信号伝達と細胞生存を調節する
1Cellular Pathobiology Unit, Plasticity and Development Section, Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, MD 21224, USA. thayashi@intra.nida.nih.gov
Cell
|November 6, 2007
まとめ
ER-ミトコンドリアのインターフェースにあるシグマ-1受容体 (Sig-1R) は,カルシウムシグナリングを調節する. BiPからのSig-1R解離はミトコンドリアのカルシウム吸収を高め,細胞生存とERストレス反応に影響を与えます.
科学分野:
- 細胞生物学 細胞生物学
- ミトコンドリア機能
- エンドプラズマ網膜のダイナミクス
背景:
- エンドプラズマ網膜 (ER) とミトコンドリアのコミュニケーションは,細胞のエネルギー生産と生存に不可欠です.
- ミトコンドリア関連ER膜 (MAM) は,イノシトール1,4,5-トリフォスファート受容体 (IP3Rs) 経由でERからミトコンドリアへの直接カルシウム (Ca2+) 転送を促進します.
研究 の 目的:
- ERタンパク質シグマ-1受容体 (Sig-1R) がER-ミトコンドリア通信の調節体としての役割を調査する.
- Sig-1RがMAMでカルシウムシグナル伝達を調節するメカニズムを解明する.
主な方法:
- MAMにおけるCa2+感受性およびリガンド操作受容体チャペロンとしてのSig-1Rの特徴.
- 異なるER Ca2+条件下でBiPとSig-1R複合体の形成の分析.
- 慢性的なERストレス下でのSig-1R転位の評価.
- ERストレス反応とアポトーシスに対するSig-1Rレベルの影響の評価.
主要な成果:
- Sig-1Rは,MAMでCa2+感受性およびリガンド操作のチャペロンとして機能します.
- Sig-1Rは通常,MAMでBiPと複合する;解離は,ER Ca2+の枯渇またはリガンドの刺激により発生する.
- Sig-1R解離は,IP3R経由でミトコンドリアへのCa2+シグナル伝達を延長する.
- Sig-1Rは慢性的なERストレス中に転位することができ,そのレベルは細胞の運命を左右します (ストレスに対抗またはアポトーシスを強化します).
結論:
- Sig-1Rを含むMAMのERチャペロン機械は,ER Ca2+レベルを感知する.
- この感知メカニズムは,ER-ミトコンドリアCa2+シグナル伝達と最終的には細胞生存を調節する.
- Sig-1Rは,臓器間の通信を調節することによって,ストレス下での細胞の恒常性を維持する上で重要な役割を果たします.
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