ラトロフィリンGPCRは,FLRTとテヌリンの結合による直接シナプス特異性
Richard Sando1, Xian Jiang1, Thomas C Südhof2
1Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|February 23, 2019
まとめ
細胞粘着分子はシナプスの形成を誘導する. ラトロフィリン3は,Gタンパク質結合受容体であり,フィブロネクチンレウシンに富んだ重複型膜タンパク質 (FLRTs) とテヌリンとの結合が求められ,特定のヒポカンプスシナプスを形成する.
科学分野:
- 神経科学
- 分子生物学
- 細胞生物学
背景:
- 細胞粘着分子はシナプスの形成に不可欠な双方向信号を媒介する.
- シナプスの特異性の基礎となる正確なメカニズムは,ほとんど不明である.
研究 の 目的:
- 海馬の神経細胞における特定のシナプス形成を誘導する粘着Gタンパク質結合受容体 (GPCRs) の役割を明らかにする.
- シナプスの発達におけるラトロフィリン-3とそのリガンドとの分子相互作用を調査する.
主な方法:
- シナプスの形成に関する in vivo 研究に変異性マウスを使った.
- リガンド結合の機能的効果を評価するために in vitro ニューロン培養を用いる.
- ラトロフィリン3とフィブロネクチンレウシンに富んだ重複型トランスメブランタンパク質 (FLRT) とテヌリンとの結合相互作用を研究した.
主要な成果:
- ラトロフィリン2とラトロフィリン3は,ヒポカンパのCA1ニューロンにおける,それぞれ,穿孔経路とシャッファー・コラーテル・シナプス形成を選択的に誘導する.
- ラトロフィリン3がFLRTとテヌリンの両方に結合することは,インビボにおける入力特異なシナプス形成に不可欠である.
- テヌリンとFLRTの併用は,個別にではなく,強力に刺激性シナプス形成をインビトロで誘導する.
結論:
- ポストシナプスラトロフィリンは,異なるプレシナプスリガンドの同時結合により,刺激性シナプス形成をオーケストラする.
- この二重リガンド結合メカニズムは,正確なデンドリット位置にシナプス入力を確立するために重要です.
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