TSC複合体の空間的制御は,リンと栄養の調節を統合し,ライソソームのmTORC1でmTORC1を調節する
Suchithra Menon1, Christian C Dibble2, George Talbott1
1Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Cell
|February 18, 2014
まとめ
インスリンシグナル伝達は,TSC複合体を調節することによって細胞の成長を制御します.
科学分野:
- 細胞生物学 細胞生物学
- 分子シグナル伝達です.
- メタボリック調節 メタボリック調節
背景:
- ラパミシン複合体1 (mTORC1) 経路のメカニスティックターゲットは,細胞の成長を調節する.
- インスリンはPI3K-Akt経路を通じてmTORC1を活性化させ,TSC複合体を抑制してRheb.を活性化させます.
- mTORC1の調節と栄養素感知および成長因子経路の統合は不明である.
研究 の 目的:
- インスリンシグナル伝達がmTORC1.1.を制御するために栄養素感知経路と統合するメカニズムを解明する.
- mTORC1の活性化におけるTSC複合体の局所化の役割を調査する.
主な方法:
- TSC複合体,Rheb,mTORC1.1.の細胞局所化研究を行いました.
- TSC2.2のAkt媒介によるリン酸化の分析.
- mTORC1シグナル伝達に対するPTEN機能喪失の影響の調査.
主要な成果:
- インスリンがTSC複合体とリソソーム表面の急性解離を誘導する.
- TSC複合体は,レブ依存的な方法でリソソームと結合する.
- アクト媒介のTSC2リン酸化は,インスリン刺激によるTSC複合体の解離に必要である.
- PTENの喪失は,Aktに依存したTSC複合体の解離を経由して構成的なmTORC1の活性化につながります.
結論:
- TSC複合体とmTORC1からリヘブへの空間的なリクルートメントは,リソソームで多様な成長信号を統合します.
- これは,インスリンと栄養素の利用可能性によるmTORC1の調節のための統一メカニズムを提供します.
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