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電路配線におけるテヌーリンの機能の構造的基礎:シナプスの毒素モチーフ
Jingxian Li1, Moran Shalev-Benami2, Richard Sando3
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL 60637, USA.
Cell
|April 21, 2018
まとめ
発育に不可欠なテヌリン (TEN) は,細菌の毒素と構造的に類似しています. TEN2における代替スプライシングは細胞の結合とシグナル伝達を調節し,神経の発達に影響を与える.
科学分野:
- 構造生物学
- 神経科学
- 細胞の粘着
背景:
- テンウリン (TEN) は,組織発育と軸索誘導に不可欠な細胞表面粘着タンパク質です.
- その正確な構造的メカニズムと規制機能は まだ十分に理解されていない.
研究 の 目的:
- 人間のTEN2細胞外領域 (ECR) の構造的組織を解明する.
- TEN2機能における代替スプライシングの役割とラトロフィリン (LPHN) との相互作用を調査する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) で,ヒトのTEN2 ECRの3.1-Å構造を決定する.
- 細胞間粘着とシグナル伝達への影響
主要な成果:
- TEN2 ECRは,バクテリアのTc-トキシンに似た,βバレル,免疫グロブリンのようなドメイン,およびβプロペラを持つユニークな構造を示しています.
- βプロペラ内の交互にスプライスされた領域は,制御スイッチとして機能します.
- 1つのスプライス変種はLPHN依存の細胞間信号伝達を促進し,もう1つは阻害性ポストシナプス分化を引き起こす.
結論:
- TENの異常な構造は,細胞プロセスにおけるその多様な役割の根底にある.
- TEN2の代替スプライシングは,ラトロフィリン受容体と相互作用し,細胞の結合と神経の発達を調節するメカニズムを提供します.
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