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SAMTORはmTORC1経路のためのS-アデノシルメチオニンセンサーです

Xin Gu^1,2,3,4, Jose M Orozco^1,2,3,4, Robert A Saxton^1,2,3,4

¹Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Science (New York, N.Y.)

|November 11, 2017

まとめ

SAMTORは新しいタンパク質で,S-アデノシルメチオニン (SAM) のセンサーとして作用し,メチオニンの代謝をmTORC1のシグナル伝達と結びつける. SAM濃度が低い場合,mTORC1を抑制し,細胞成長の調節を促進する.

科学分野:

細胞生物学
メタボリズム
信号変換

背景:

mTOR複合体1 (mTORC1) は細胞の成長と代謝の重要な調節体である.
栄養素の利用性は,Rag GTPasesとリソソームの局所化を通してmTORC1の活性に影響する.
mTORC1のアップストリームレギュレータを理解することは,環境のシグナルに対する細胞の反応を解読するのに不可欠です.

研究の目的:

mTORC1シグナル伝達の新しいレギュレータを特定し,特徴づけること.
メチオニンの代謝がmTORC1の活性に影響するメカニズムを解明する.
SAMTORタンパク質が栄養素を検出する役割を調査する

主な方法:

SAMTORの結合パートナーを特定するためのタンパク質相互作用研究.
SAMTORとS-アデノシルメチオニン (SAM) の結合運動を決定する生化学的測定法.
メチオニンの利用可能性とSAMTOR操作に対する反応としてmTORC1のシグナリングを評価する細胞実験.

主要な成果:

SAMTORは,Rag GTPase活性化タンパク質であるGATOR1と相互作用することで,mTORC1のシグナル伝達を阻害するものであることが確認された.
S- アデノシルメチオニンはSAMTORに直接結合し,SAMTOR- GATOR1複合体を破壊する.
メチオニンの飢餓は,細胞内のSAMレベルを低下させ,SAMTOR- GATOR1結合を促進し,SAMTORに依存した方法でmTORC1シグナリングを阻害する.

結論:

SAMTORはSAMのセンサーとして機能し,メチオニンと単炭素代謝を直接mTORC1のシグナル伝達と結びつける.
SAMTORのSAM結合能力はメチオニン誘発 mTORC1の活性化に不可欠である.
SAMTORは,代謝状態と細胞成長の調節の間の新しい分子リンクを表しています.

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