mTORC1アクティベーター SLC38A9は,リソソームから必須アミノ酸を排出し,タンパク質を栄養素として使用するために必要です

Gregory A Wyant¹, Monther Abu-Remaileh¹, Rachel L Wolfson²

¹Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.

Cell

|October 21, 2017

まとめ

アルギニンはリソソームタンパク質SLC38A9を通じてmTORC1経路を活性化させ,リソソームから細胞成長のための必須アミノ酸の放出を調節する.

科学分野:

細胞生物学
生物化学
分子生物学

背景:

ラパミシン複合体1 (mTORC1) キナーゼのメカニスティックターゲットは,栄養素の可用性に対応する細胞成長の重要なレギュラーです.
リンソームアミノ酸の感知と輸送は細胞の恒常性にとって重要であるが,その基礎となるメカニズムは未だに完全に理解されていない.

研究の目的:

アミノ酸センシングとmTORC1の活性化におけるSLC38A9の機能を明らかにする.
アミノ酸輸送と細胞代謝におけるSLC38A9の役割を調査する.

主な方法:

mTORC1のアルギニンセンサーとしてのSLC38A9の検証
溶解体からの必須アミノ酸のSLC38A9媒介輸送の分析
臓腫瘍形成におけるSLC38A9の役割の評価

主要な成果:

SLC38A9はアルギニンセンサーとして機能し,アルギニンの可用性をmTORC1の活性化に結びつける.
SLC38A9は,ライソソームからルシンを含む必須アミノ酸の放出を促進する.
mTORC1の活性化には,SLC38A9経由でリゾソームから放出されたルシンが必要である.
臓がん細胞は,マクロピノサイト化された栄養素を利用して,腫瘍の成長のためにSLC38A9に依存しています.

結論:

アルギニンは,SLC38A9を介して,mTORC1の活動を調節するリソソームメッセンジャーとして作用する.
SLC38A9はアミノ酸ホメオスタシスと栄養素主導の細胞成長に不可欠です.
SLC38A9をターゲットにすることで,栄養素の取り除きに依存する癌の治療戦略を提供することができます.

キーワード:

アミノ酸センシングオートファジーリソソーム mTOR についてマイクロピノサイトーシス栄養素センサー

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