後シナプスシナプトタグミンは,LTP中のAMPA受容体エクソシトーシスを媒介する
Dick Wu1,2,3, Taulant Bacaj1, Wade Morishita2,3
1Department of Molecular &Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305, USA.
Nature
|March 30, 2017
まとめ
シナプトタグミン-1とシナプトタグミン-7は,学習と記憶の重要なプロセスである長期増強 (LTP) 中のAMPA受容体エクソサイトーシスを促進する余剰カルシウムセンサーとして作用します.
科学分野:
- 神経科学
- 分子生物学
背景:
- 長期増強 (LTP) は,NMDA受容体の活性化と,その後のカルシウム流入により,シナプス結合を強化する.
- LTP誘導中のカルシウムの流入は,シナプスAMPA受容体の募集を刺激しますが,その背後にあるメカニズムは不明です.
研究 の 目的:
- LTP中のカルシウム依存のAMPA受容体の募集におけるシナプトタグミンの役割を解明する.
主な方法:
- ネズミのヒッポカンパのCA1ピラミッドニューロンにおけるLTPに対するシナプトタグミン-1 (Syt1) とシナプトタグミン-7 (Syt7) の発現を阻害する効果を研究した.
- タンパク質機能を評価するために,ワイルド型およびCa2+結合欠乏Syt7変異体,および支配的な陰性Syt1変異体を使用した.
主要な成果:
- Syt1とSyt7の同時封鎖はLTPを無効化したが,単独封鎖はそうではなかった.
- LTPは野生型Syt7によって回復したが,Ca2+結合欠陥の変異体によって回復せず,カルシウム結合の必要性を示す.
- 支配的な陰性Syt1変異体の発現は,Ca2+依存のポストシナプスAMPA受容体エクソサイトーシスを抑制し,LTPを阻害した.
結論:
- 後シナプスSyt1とSyt7は,LTPの間,AMPA受容体のエクソサイトーシスのカルシウムセンサーとして冗長的に機能する.
- これは,シナプス性可塑性,学習,記憶に不可欠なAMPA受容体の新規メカニズムを特定しています.
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