TFEBは,オートファギーをリソソームバイオゲネシスと結びつける

Carmine Settembre¹, Chiara Di Malta, Vinicia Assunta Polito

¹Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.

Science (New York, N.Y.)

|May 28, 2011

まとめ

飢餓は,オートファギーと呼ばれる細胞過程を誘発し,オートファゴソームとリソソームの調整によって分解を高めます. これは,転写因子EB (TFEB) と栄養素に敏感なキナーゼ経路によって制御されます.

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.
バイオケミストリーバイオケミストリー

背景:

オートファギーは,オートファゴソームとリソソームを伴う基本的な細胞の分解過程です.
細胞の飢餓は,これらの臓器細胞を膨らませることで,分解を高めます.
この協調反応を調節する正確な分子機構は,現在調査中です.

研究の目的:

飢餓によって活性化され,オートファギーを制御する転写プログラムを解明する.
飢餓中のオートファゴソームとリゾソームの機能を調整する重要な調節体を特定する.
この重要な調節器の活動を制御するシグナル伝達経路を調査する.

主な方法:

飢餓に誘発された遺伝子を特定するための転写プロファイリング.
リゾソームおよびオートファジック遺伝子発現の分析.
タンパク質の局所化とリン酸化を評価するために,ウェスタン・ブロッティングと免疫光学.
信号伝達経路の薬理学的抑制と遺伝子操作.

主要な成果:

飢餓は,オートファゴソーム形成,リソソーム-オートファゴソーム融合,および基板の分解を制御する転写プログラムを活性化します.
リンソームバイオゲネシスの主要な調節体である転写因子EB (TFEB) が,このプログラムを調整しています.
細胞外信号調節キナーゼ2 (ERK2) はTFEBをリン酸化し,その核の局所化と活性を調節する.
ERK2の活動は,細胞外栄養素レベルによって調節され,栄養素感知とオートファギーを結びつける.

結論:

ミトゲン活性化タンパク質キナーゼ (MAPK) に依存する経路がオートファギーを調節する.
この経路は,リソソームとオートファゴソームの生体生成と,それらの機能的なパートナーシップの両方を制御します.
TFEBは,栄養素の利用可能性に応じて,リゾソームとオートファージの経路を統合する中心的なコーディネーターとして機能します.

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