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S-ゲラニルゲラニル-L-グルタチオンは,ヒトB細胞受容体P2RY8のリガンドである
Erick Lu1, Finn D Wolfreys1, Jagan R Muppidi1,2
1Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Nature
|March 8, 2019
まとめ
研究者らは,S-ゲラニルゲラニル-L-グルタチオン (GGG) をP2RY8受容体の新型リガンドとして特定し,生殖中心のB細胞収束の調節に不可欠であり,B細胞悪性腫瘍に関与している.
科学分野:
- 免疫学とがん生物学
- 分子生物学と細胞生物学
背景:
- ゲルミナルセンターは適応免疫に不可欠ですが,B細胞がんにも関連しています.
- 運動性生殖中心のB細胞を卵泡内に閉じ込めているメカニズムは完全に理解されていません.
- B細胞の移動と成長に関与するP2RY8受容体は,B細胞リンパ腫で頻繁に変異します.
研究 の 目的:
- P2RY8受容体の未知のリガンドを特定する.
- P2RY8のシグナル伝達が生殖中心組織とB細胞の悪性腫瘍における役割を明らかにする.
主な方法:
- 生物学的サンプルと細胞上浮体におけるP2RY8リガンドのスクリーニング
- 新生物分子を特定するための生化学分化と質量スペクトロメトリー
- 細胞の移動,シグナル伝達,受容体の活性化を in vitro と in vivo で評価する機能検査
主要な成果:
- S- ゲラニルゲラニル- L- グルタチオン (GGG) は,リンパ性組織に存在する強力なP2RY8リガンドとして特定されました.
- GGGはゲルミナルセンターのB細胞と葉っぱのTヘルパー細胞のケモカイン媒介による移行を阻害した.
- ガンマグルタミルトランスフェラーゼ5 (GGT5) はGGGを代謝し,その過剰発現はP2RY8媒介のB細胞収束を妨げました.
結論:
- GGGは細胞間シグナル伝達分子で,B細胞の移動を制御することで生殖中心の反応を組織する.
- GGT5はGGGグラデントを確立し,リンパ性組織内のB細胞の局所化を調節する.
- GGGとP2RY8のシグナリングは,B細胞悪性腫瘍および他の癌の治療標的を代表する可能性があります.
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