リソソーム酵素輸送因子LYSETは,細胞外タンパク質の栄養利用を可能にします
Catarina Pechincha1,2, Sven Groessl1,2, Robert Kalis3,4
1Cell Signaling and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Science (New York, N.Y.)
|September 8, 2022
まとめ
哺乳類の細胞は細胞外タンパク質を アミノ酸に利用し 癌の成長に不可欠なプロセスです 研究者らは,LYSET (TMEM251) がリソソムの酵素の輸送と栄養素の吸収に不可欠であると特定し,がん代謝とリソソムの貯蔵障害におけるその役割を明らかにした.
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- 哺乳類の細胞は,マクロピノシトーシスと細胞外タンパク質の溶解体分解によってアミノ酸を合成することができる.
- 癌細胞は栄養が限られた腫瘍の微小環境で この経路を利用して成長します
研究 の 目的:
- 細胞外タンパク質をアミノ酸源として利用するために重要なタンパク質を特定する.
- LYSET (TMEM251) の分子メカニズムを細胞の栄養吸収とリソソーム機能で解明する.
主な方法:
- 重要な遺伝子を特定するために,定義された栄養条件下で遺伝子スクリーニングが行われました.
- ゴルギ装置でのタンパク質関連研究が行われました.
- LYSET欠乏細胞でライソソーム酵素活性と貨物の周回を評価した.
主要な成果:
- LYSET (TMEM251) は,細胞外タンパク質を消費するために選択的に必要とされるトランスメブランタンパク質として特定されました.
- LYSETは,GolgiにおけるGlcNAc-1-phosphotransferaseと結合し,それを安定させる.
- LYSET欠乏症は,リソソーム酵素の減少とマクロピノサイトとオートファージの転移の障害を引き起こします.
結論:
- LYSETはリソソムの酵素輸送経路の重要な構成要素です.
- LYSET機能障害は遺伝性溶解体貯蔵障害の病理に寄与する.
- LYSETは,がん細胞の代謝適応を阻害する治療標的である可能性があります.
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