Tリンパ球におけるカルシウムシグナル伝達の調節は,第2のメッセンジャーサイクルであるADP-リボースによって行われる
A H Guse1, C P da Silva, I Berg
1Department of Enzyme Chemistry, Institute of Physiological Chemistry, University of Hamburg, Germany. guse@uke.uni-hamburg.de
Nature
|March 17, 1999
まとめ
循環性ADP-リボース (cADPR) は,Tリンパ球における重要な第2のメッセンジャーとして作用し,カルシウムシグナル伝達とT細胞活性化を調節する. この研究では,cADPRがcADPRであることを確認しました.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- 循環性ADP-リボース (cADPR) は,真核細胞内のカルシウムイオンを動員することが知られている.
- Tリンパ球における第2のメッセンジャーとしての役割は,まだ完全に理解されていません.
- T細胞の活性化には,カルシウム動員を含む複雑なシグナル伝達経路が含まれます.
研究 の 目的:
- Tリンパ球における第2のメッセンジャーとして循環性ADP-リボース (cADPR) を確立する.
- T細胞受容体/CD3 (TCR/CD3) の複合媒介信号伝達におけるcADPRの役割を調査する.
- T細胞におけるcADPR作用の分子メカニズムを解明する.
主な方法:
- 高性能液体クロマトグラフィー (HPLC) は,細胞内cADPRレベルを測定する.
- TCR/CD3複合体によるT細胞刺激.
- シグナル伝達阻害を評価するために,cADPRアンタゴニストの使用.
- T細胞の増殖と活性化マーカーの分析 (CD25,HLA-DR).
- [3H]ライオノジンを使用して,ライオノジン受容体相互作用を研究するために,放射性リンガンド結合測定法.
主要な成果:
- TCR/CD3刺激はADP-リボシルサイクラスを活性化し,細胞内cADPRレベルを上昇させます.
- cADPRの増加は,持続的なカルシウムシグナル伝達とT細胞活性化と因果的に関連しています.
- cADPRアンタゴニストは,TCR/CD3誘発カルシウムシグナル伝達,増殖,活性化マーカー発現を抑制する.
- cADPRの標的であるタイプ3ライオノジン受容体は,T細胞で発現する.
- cADPRは3型ライオノジン受容体の活性を直接調節する.
結論:
- 循環性ADP-リボース (cADPR) は,ヒトT細胞における重要な第2メッセンジャーである.
- 3型ライオノジン受容体を含むcADPR/カルシウムシグナル伝達経路は,T細胞活性化に極めて重要です.
- この経路は,T細胞の反応を調節する潜在的治療標的である.
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