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活性化されたTリンパ球の分裂後の細胞非対称性の代謝維持
Katherine C Verbist1, Cliff S Guy1, Sandra Milasta1
1Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Nature
|April 12, 2016
まとめ
非対称なT細胞分裂により 異なる子細胞が生じる. 転写因子c- MycとmTORC1のような代謝経路は,これらの違いを確立し維持するために協力し,細胞の運命に影響を与えます.
科学分野:
- 免疫学
- 細胞生物学
- 発達生物学
背景:
- 不対称な細胞分裂は様々な生物の分化と発達に不可欠である.
- 活性化されたTリンパ球は非対称的に分裂し,エフェクタのような子細胞と記憶のような子細胞を生成します.
- 転写因子c-Mycは T細胞増殖に不可欠な代謝再プログラムを駆動する.
研究 の 目的:
- アシンメトリックなT細胞分裂におけるc-Mycの役割を調査する.
- c-Myc,代謝再プログラム,T細胞における細胞運命を決定する関係を探求する.
- T細胞分裂後のメタボリックシグナル伝達経路が異なる細胞の運命にどのように影響するかを理解する.
主な方法:
- マウスの活性化されたT細胞における非対称的な細胞分裂を研究した.
- c-Myc,アミノ酸トランスポーター,およびアミノ酸含有量の分布を分析した.
- ラパミシン複合体1 (mTORC1) の哺乳類標的の活性を評価した.
- mTORC1の活性とc-Mycの発現を実験的に操作した.
主要な成果:
- c-Mycは活性化されたT細胞の最初の分裂時に非対称に分布しています.
- 非対称なc- Myc濃度,アミノ酸トランスポーター,アミノ酸含量,mTORC1活性との間にある相関が観察された.
- アミノ酸とmTORC1の活性が,子細胞間の異なるc- Myc発現を維持することを実証した.
- 非対称なc- MycレベルはT細胞の増殖,代謝,分化に影響を及ぼすことが示された.
結論:
- メタボリックシグナル伝達経路と転写プログラムは,非対称なT細胞分裂に続く異なる細胞運命を維持するために協力します.
- 非対称なc- Myc分布は,子T細胞における差異的な結果を引き起こす重要なメカニズムである.
- mTORC1の活性とアミノ酸の可用性は,非対称なc- Mycレベルと,その後の細胞運命を決定する上で重要な役割を果たします.
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